Genetic Testing of Fetal Loss of Heterozygosity Using Single Nucleotide Polymorphism Array and Whole Exome Sequencing

Genetic Testing of Fetal Loss of Heterozygosity Using Single Nucleotide Polymorphism Array and Whole Exome Sequencing | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Article Genetic Testing of Fetal Loss of Heterozygosity Using Single Nucleotide Polymorphism Array and Whole Exome Sequencing Huili Xue, Aili Yu, Lin Zhang, Lingji Chen, Qun Guo, Min Lin, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3137002/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 25 Jan, 2024 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract Background To explore the clinical significance of fetal loss of heterozygosity (LOH), identified by single-nucleotide polymorphism array (SNP array). Methods We retrospectively reviewed data form pregnant women who underwent invasivediagnostic procedure at prenatal diagnosis centers in Southeastern China from December 2016 to December 2021. SNP array was performed by the Affymetrix CytoScan 750K array platform. Fetuses with LOH (10 Mb as the threshold or over 5 Mb involving imprinted chromosomes) were further identified by parental verification, MS-MLPA, and/or trio whole exome sequencing (trio-WES), and the genetic results, fetal clinical manifestations, and perinatal outcome were comprehensively analyzed. Results Of 11 062 fetuses, 106 (0.96%) with LOH exhibiting a neutral copy number were detected; in 88 (83.0%) of these, LOH occurred in a single chromosome, while 18 (17.0%) fetuses had multiple LOHs on different chromosomes. A total of 66 fetuses had ultrasound anomalies (UAs); the most frequent UA was fetal growth restriction (18/66 (27.3%)). Further genetic analysis was performed in 42 cases (21 cases by parental SNP array verification and 21 cases by trio-WES), in which, we found clinically relevant uniparental disomy in 12 cases, pathogenic variants in five cases, likely pathogenic variants in four cases, variant of unknown significance in six cases, and identity by descent in eight cases. Significantly, the rate of adverse pregnancy outcomes in fetuses with LOH and UAs (24/66 (36.4%)) was higher than in those without UAs (6/40 (15.0%)) ( p < 0.05). Conclusions Fetuses with LOH is not uncommon. Various molecular genetic testing techniques, such as parental SNP array verification, trio-WES, MS-MLPA, regular and systematic ultrasonic monitoring, and the placental study when necessary, should be performed to accurately assess the prognosis of fetal LOH and guide the affected pregnancy management. Biological sciences/Genetics Health sciences/Medical research Health sciences/Molecular medicine loss of heterozygosity prenatal diagnosis single nucleotide polymorphism array uniparental disomy whole exome sequencing Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Background In the prenatal diagnostic setting, chromosomal microarray analysis (CMA) improved the diagnostic rate for chromosomal abnormalities by 4.1–10% compared with traditional karyotyping in fetuses with ultrasound anomalies (UA). Single nucleotide polymorphism array technology can not only identify copy number variation (CNV) but also detect chromosome aneuploidy and haploidy, triploidy, loss of heterozygosity (LOH), uniparental disomy (UPD), and low-level mosaicism 1,2 . LOH, referred to as the region of homozygosity in a chromosome, and concerns identity by descent (IBD) and UPD. When LOH is confirmed to have been inherited from only one parent, it is called UPD, which can lead to imprinting disorders involving imprinted chromosomes 6, 7, 11, 14, 15, and 20. Moreover, UPDs were classified as either isodisomy, heterodisomy, or mixed UPD, according to the parental origin. Common mechanisms resulting in UPD include trisomy rescue, monosomy rescue, and somatic mitotic recombination, resulting in mosaic segmental UPD 3,4 . It is challenging to assess the prognosis of fetuses with LOH in prenatal diagnosis. Thus, understanding its clinical significance is necessary due to the phenotypic complexity of LOH and its uncertain pathogenicity. To assess the clinical significance and better understand the correlation between LOH and its phenotype, we investigated the clinical manifestations, performed further molecular genetic analysis using parental SNP array verification, trio whole exome sequencing (WES) and Methylation-specific multiplex ligation dependent probe amplification (MS-MLPA), and tracked the perinatal outcomes of fetuses with LOH. Patients and methods Subjects We retrospectively reviewed pregnant women undergoing invasive diagnostic procedure for a variety of indications at all prenatal diagnosis centers in Fujian Province in southeastern China, Fujian Medical University, China, from December 2016 to December 2021. Most of the cases came from Fujian Maternity and Child Health Hospital. Obtaining informed consent from all the pregnant couples, fetal samples were collected via invasive diagnostic procedure according different weeks of gestation. The study was approved by the Ethics Committee of the Fujian Maternity and Child Health Hospital (No.2016KYLLD01051). Conventional karyotyping analysis Karyotyping was performed following the standard cytogenetic protocol, and karyotypes were scanned on Leica GSL120. At least 20 metaphases were counted, and five metaphases were analyzed. Karyotype analysis and description were based on ISCN 2020. Isolation of genomic DNA Fetal sample, 15 mg of chorionic villi, 30-40 mL of amniotic fluid, or 2-5 mL umbilical cord blood was obtained, and genomic DNA from the fetus and its parents were extracted using the QIAamp® DNA Blood Mini Kit (Qiagen Inc., Hilden, Germany) following the manufacturer’s instructions, and maternal cell contamination was ruled out using microsatellite DNA linkage analysis. S ingle nucleotide polymorphism array and data analysis Chromosomal aberrations, CNVs and LOH were detected using a SNP array on a CytoScan 750K (Affymetrix Inc., Santa Clara, CA) platform containing 200 000 SNPs and 550 000 CNVs probes, all the experimental processes of SNP array were performed as previously described 5 . After obtaining informed consent, parental SNP array verification was performed to confirm the origin of fetal LOH. The raw data were analyzed using the Affymetrix Chromosome Analysis Suite software (version 3.1.0.15). The coordinate of the chromosome was described based on the genome version hg19. CNVs were classified according to the American College of Medical Genetics (ACMG) guidelines 6 . The reporting threshold was set at CNV ≥ 500 Kb and 10 Mb size as the threshold of LOH or over 5 Mb for a terminal fragment LOH occurred in imprinted chromosomes (chromosome 6, 7, 11, 14, 15 and 20). The significance of LOH results was interpreted through PubMed (http://www.ncbi.nlm.nih.gov/pubmed), Online Mendelian Inheritance in Man (OMIM; http://www.omim.org/), DECIPHER (https://decipher .sanger.ac.uk/), UCSC (http://genome.ucsc.edu/), ClinGen Dosage Sensitivity Map (https://www.ncbi.nlm.nih.gov/projects/dbvar/clingen/index.shtml), uniparental disomy (http://cs-tl.de/DB/CA/UPD/0-Start.html), Geneimprint (http://www.geneimprint.com/), the Catalogue of Imprinted Genes (www.otago.ac.nz/IGC), the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk/ac/index.php), the Locus-Specific Mutation Database (http://www.hgvs.org/dblist/glsdb.htm) and the 1000 Genomes Project Dataset (https://www.ncbi.nlm .nih.gov/variation/tools/1000genomes/). WES and bioinformatics analysis To identify homozygous mutations of recessive diseases in addition to UPD, trio-WES (for fetuses and parents) was carried out with the informed consent of pregnant couples. After the sample genomic DNA was extracted, exon capture was conducted using Agilent Sure Select Technology (Agilent, Santa Clara, CA, USA), fragmented randomly, purified, and enriched to construct DNA libraries. Paired-end sequencing was performed on Illumina HiSeq 2500 (Illumina, USA) instruments according to the manufacturer’s instructions (Illumina, San Diego, CA, USA). For sequence alignment, variant calling, and annotation, the sequences were mapped to their location with the human genome reference sequence (hg19 build) using Burrows-Wheeler software (version 0.59) 7 . All SNVs and InDels were annotated with public population frequency databases, including NCBI dbSNP, 1000 Genomes Project, the Exome Aggregation Consortium, as well as OMIM, Swiss-var, Human Gene Mutation Database, ClinVar, and other disease databases, and only variants that were clinically or potentially relevant to the patients’ phenotype were reported. Annotation of mutations, prediction of protein function effects and shear harmousness were conducted and the pathogenicity of the variants was assessed according to ACMG 8 . MS-MLPA Methylation analysis of 7q21.13q36.3 loci was performed by MS-MLPA (SALSA MS-MLPA probe mix ME030-C3 BWS/RSS (MRC Holland, Amsterdam, The Nederland’s)), and the relative copy numbers of the three methylation probes in the MEST gene (maternal methylation gene region, paternal methylation was preferentially expressed) on chromosome 7q32.2 was determined. All procedures were performed following the manufacturers’ protocols performed as previously described 9 . Pregnancy outcome In fetuses with LOH, we collected data relating to basic information, imaging findings, serological Down's screening results, non-invasive prenatal testing (NIPT) results, results of invasive diagnostic testing, further genetic analysis, perinatal outcomes, and follow-up information. Perinatal outcomes were obtained from delivery records in our hospital. Otherwise, data relating to other cases from other centers were followed up via telephone. Statistical analysis SPSS software version 22.0 (SPSS, Inc., Chicago, IL) was used for statistical analysis. Measurement data were expressed as mean ± standard deviation, statistical comparisons were performed using χ 2 test and Fisher’s exact test, p < 0.05 was considered statistically significant. Results Patient characteristics A total of 11062 fetuses undergoing invasive diagnostic testing over a period of 5 years were analyzed using SNP array, and there were 106 fetuses with LOH. The detection rates of fetal LOH for different invasive diagnostic indications are depicted in Table 1. The mean weeks of gestation and maternal age for pregnancies with fetal LOH was 21±1 (range, 11 +6 to 31) and 31±3 (range, 19–42) years, respectively. The detailed parental SNP array verification results, trio-WES results, MS-MLPA result, ultrasound findings, and perinatal outcomes of 42 fetuses with LOH are summarized in Table 2, and the data regarding the remaining 64 prenatally diagnosed cases with LOH that declined further genetic testing are listed in Table 3. Fetal LOH detected by SNP array The overall flow of fetal LOH analysis is illustrated in Fig. 1. The detection rate of fetuses with LOH ≥ 10 Mb or ≥ 5 Mb involving imprinting regions was 0.96% (106/11 062). In 88 (83.0%) fetuses, LOH occurred on a single chromosome, while in 18 (17.0%) fetuses, multiple LOHs were detected on different chromosomes. Of the 18 cases with multiple LOHs, two cases (Cases 1 and 64) were confirmed from consanguineous couples, and the remaining 16 cases denied consanguineous miscarriage. When LOH occurred on a single chromosome, chromosomes 6 (11.4% (10/88)), 3 (10.2% (9/88)), and 5 (8.0% (7/88)) were the most frequently involved, followed by chromosomes 15 (6.8% (6/88)), 2 (6.8% (6/88)), 8 (6.8% (6/88)), and 13 (6.8% (6/88)) (Tables 2 and 3). LOH identified almost the entire chromosome in seven cases, and the involved chromosomes were chromosomes 2, 6, 13, 14, 18, and 22. In other cases, LOH occurred in a partial fragment of the chromosome, ranging from 5.18 Mb to 96.8 Mb. In total, four cases of mosaic LOH were identified, including in chromosomes 13 and 14, 5q11.1q35.3, and 7q21.13q36.3, respectively. The mosaicism rate ranged from 30% to 80%. Both cases (Cases 22 and 28) with LOH on the entire chromosome 6 presented with fetal growth restriction (FGR), and were further diagnosed as paternal UPD6 and maternal UPD6, respectively. Finally, both patients elected termination of pregnancy (TOP) (Table 2). Isolated segmental LOH on chromosome 6 was identified in 10 cases, of which nine presented with UAs, including FGR, thickened nuchal translucency (NT), enhanced bowel echo, intracardiac echogenic focus, increased umbilical artery resistance index, oligohydramnios, cervical lymphatic hygroma, mild regurgitation of tricuspid valve, fetal bilateral renal enlargement, increased renal echogenicity, reverse a-wave of ductus venosus, and enhanced intestinal echo, resulting in TOP ( n =6) and preterm birth ( n =1). The other three cases had a favorable outcome. Isolated LOH on chromosome 3 was identified in nine cases, of which only two presented with UAs, including thickened NT, resulting in abortion ( n =1). The other seven cases showed no anomalies on prenatal ultrasound and had no obvious abnormal phenotypes after birth. Isolated fetal LOH on chromosome 5 was identified in seven cases, of which three all had abnormal ultrasound findings, including FGR, small fetal head circumference (HC) for gestation age, lethal bone dysplasia (osteogenesis imperfecta type II), micrognathia, small biparietal diameter (BPD), HC, and femur length (FL) for gestation age, bilateral femoral curvature, less than the normal predictive value -2SD, hydrops fetalis, fetal giant bladder, fetal lung cystic adenoma, resulting in TOP (n=3) or preterm birth (n=1), and missed abortion (n=2); the other case (Case 34) showed minor abnormal phenotypes on prenatal ultrasound, and presented micrognathia after birth. UAs in fetal LOH detected by SNP array Totally, 66 fetuses presented UAs, including 22 (33.3%) with structural abnormalities, 24 (36.4%) with ultrasonic soft marker, 18 (27.3%) with FGR and 9 (13.6%) with other presentations. The most common soft marker anomaly was thickened NT. The most frequent ultrasonic structural anomalies were cardiovascular (9.1%), skeletal (6.1%), and genitourinary malformations (6.1%). In the group with UAs, fetal LOH mostly involved chromosomes 5, 6, and 1, whereas LOH mostly occurred on chromosomes 3, 10, and 18 in the group without UAs (Tables 2 and 3). FGR was detected prenatally in 18 fetuses, of which 11 had FGR as an isolated ultrasound finding. The most frequently involved chromosome was chromosome 6 (n=6) in cases with FGR, followed by chromosomes 7 (n=3) and 17 (n=3). The outcomes of these 18 fetuses included TOP (n=11), preterm birth (n=3), and term birth (n=4). The incidence of fetal TOP was significantly higher in fetuses with FGR than in those without FGR (61.1% (11/18) vs 21.6% (19/88), p < 0.01) (Tables 2 and 3). UPD results To verify the parental source of fetal LOH, 21 cases of fetal LOH were confirmed by parental SNP array analysis, of which two (9.5%) had paternal UPD (Cases 4 and 22) and 12 (57.1%) had maternal UPD, namely, case 4 (UPD 14 pat), case 6 (UPD7 mat), case 14 (mosaic UPD7 mat), case 19 (UPD15 mat), case 21 (UPD 16 mat), case 22 (UPD6 pat), case 24 (UPD15 mat), case 25 (UPD11 mat), case 26 (UPD7p22.3p12.2 mat), and case 30 (UPD11 mat); four cases were confirmed to be IBDs (Cases36-42). Among the 14 cases with UPD, cases 19 and 24 were diagnosed with Prader–Willi syndrome (PWS), cases 6, 14, 25, 26, and 30 were determined Silver-Russell syndrome (SRS), cases 4 and 22 were diagnosed with Kagami-Ogata syndrome (KOS) and transient neonatal diabetes mellitus, respectively. None of confirmed imprinted genes were detected in the cases 20, 23, 27, and 28 except case 21 (UPD16 mat), thus classifying them variant of uncertain significance (VOUS). Among the 14 UPDs, notably, in case 14, amniocentesis was performed due to fetal right aortic arch with aberrant left subclavian artery as ultrasound indicated, LOH with a size of 70.4 Mb was observed in 7q21.13q36.3 by SNP array (Fig. 2A). First, parental SNP array verification indicated that it is not possible to determine whether source of the LOH on chromosome 7 is paternal or maternal (Fig. 2B); Then, MS-MLPA for the methylation analysis of 7q21.13q3615 loci revealed that the relative copy numbers of the three methylation probes (184 bp, 190 bp and 256 bp) in the MEST gene (maternal methylation gene region, paternal methylation was preferentially expressed) were 0.66, 0.66, and 0.64, respectively, suggesting a possible low proportion mosaic maternal UPD7 associated with Silver-Russell syndrome (Fig. 2C). However, the experimental result was close to the threshold range; thereby, it could not be determined and interpreted accurately. The fetus was term delivered, feeding difficulties existed after birth, 3 months after delivery at present, the child's height and development were normal, only light weight (Table 2). Twenty-one cases of fetal LOH were further verified by trio-WES, of which one (4.8%) had paternal UPD and four (19.0%) had maternal UPD. Notably, trio-WES was performed in case 12, and maternal UPD15 associated with PWS was confirmed, and the pregnancy was terminated at 28 weeks (Table 2). None of the definite imprinted genes observed in the other four UPDs, thus classifying a VOUS. Karyotyping results Karyotyping was performed successfully in all 106 fetuses with LOH. In total, 97 cases yielded normal results, and nine cases had abnormal karyotyping results, including 47,XX,+mar dn, 46,X,i(Xq)[40]/45,X[14], 46,XX,t(4;5)(q31;q23)pat, 46,XY,t(11;22)(q24.1;q12.3) dn, 47,XX,+21, mos 47,XY,+22[3]/46,XY[58], 46,XX,t(12;21)(q12;q22.2) mat, 47,XN,+mar[57]/46,XN[41] and 46,X,inv(Y)(p11.2q11.2) mos 45%. Gene mutation results Trio-WES was performed in 21 cases to detect gene mutation of autosomal recessive diseases in addition to UPD, and 11 results were clinically significant, including 5 pathogenic variants, 4 likely pathogenic variants and 2 pathogenic UPDs. Among these clinically significant results, three cases (Cases 1, 9, and 15) were identified homozygous mutations in autosomal recessive diseases attributed to LOHs by trio-WES. For case 11, fetal BPD was small for gestation age by ultrasound, SNP array showed a 38 Mb LOH in 14q13.1q24.2, prenatal trio-WES declined, the fetus was term birthed, the infant was 5 months old now, 60 cm tall, and often arches her back; brain MRI at three months of age revealed that bilateral ventricles were asymmetrical, the left lateral ventricle was larger than the right, some of the extracerebral spaces are slightly widened. Low T1W1 and high T2W1 signals were observed in the bilateral maxillary, ethmoid, and sphenoid sinus. Postnatal trio-WES indicated UPD14 was ruled out, and showed a de novo heterozygous mutation, NM_000095: c.1417_1419dup (p. D473dup), in COMP in the female infant (Fig. 3), which is an incidental finding, associated with autosomal dominant pesudoachondroplasia (PSACH, OMIM:177170), epiphyseal dysplasia, multiple, 1(EDM1, OMIM:132400), and carpal tunnel syndrome 2 (CTS2, OMIM:619161). For case 18, amniocentesis was performed, as the fetal left femur was slightly curved, and the SNP array revealed a 20 Mb LOH located in 5q23.2q32. Prenatal trio-WES indicated a de novo missense variant, NM_000088: c.1436G>C p.G479A , in COL1A1 (120150) on chromosome 17 in the fetus (Fig. 4), associated with osteogenesis imperfecta, type I (OMIM:166200), type II (OMIM:166210), type III(OMIM:259420), type IV (OMIM:166220), Ehlers-Danlos syndrome, arthrochalasia type 1 (OMIM:130060), Caffey disease (OMIM:114000), and bone mineral density variation QTL, steoporosis (OMIM:166710), and the couple elected TOP at 26 weeks. In case 29, amniocentesis was performed, as the fetal bilateral femoral curvature was less than the normal predictive value -2SD was detected on ultrasound, and the SNP array revealed a 46.1 Mb LOH located in 5p15.33p11. Prenatal trio-WES indicated an inherited paternally splicing variant, NM_000088.4: c.1615-1G>T (p. G802V), in COL1A1 (120150) on chromosome 17 in the fetus (Fig. 5), associated with autosomal dominant osteogenesis imperfecta, and the pregnancy was terminated at 23 weeks (Table 2). Perinatal outcome and follow-up The pregnancy outcomes of the 106 fetuses with LOH were as follows: 67 term births (of which two resulted in neonatal death, and one had an abnormal phenotype after birth), 29 TOPs, three preterm births, two fetal deaths, and five miscarriages. A full-term infant (Case 14) was diagnosed with feeding difficulties that existed after birth, and 3 months after delivery, the child's height and development were normal, with only low weight. A preterm infant (Case 2) was diagnosed with autism postnatally. One fetus (Case 11) showed fetal BPD that was small for gestation age on prenatal ultrasound screening and was delivered vaginally at term. The infant showed growth delay (60 cm tall at 5 months old), hypotonia, and often arched her back. The rate of adverse pregnancy outcomes in fetuses with LOH with UAs was 52.4% (22/42), while it was 32.8% (21/64) in those that did not show positive ultrasound findings ( p < 0.05). Discussion In our cohort, we investigate the clinical significance of fetal LOH as well as the correlation between fetal LOH and its clinical features. The rate of LOH meeting the report threshold in our study was 0.96%, slightly lower than the 0.97% reported by Liu et al. 10 , which might be attributed to different sample sizes of the study population and the threshold of LOH reported. The threshold in our cohort was set according to the reported study by Hoppman, et al. 11 . In addition, none of clinically significant LOHs occurring in chromosome X were reported due to lack of the adverse family history associated with X-linked disorders. Thereby fetal LOH occurred on a single chromosome, chromosomes 6 and 5 were the most common involved; whereas, Liu et al. 10 showed that LOH was more likely to occur in chromosomes X, 2 and 16. The discordance may be due to the reporting threshold of the fetal LOH studied. Clinically significant imprinting disorders should be valued, especially for UPD involving imprinted chromosomes 6, 7, 11, 14, 15 and 20 12,13 . The clinical significance of UPD is closely associated with the affected imprinted region and genes in addition to parental origin 14,15 . It is unclear whether there is an imprinting effect in UPD 16 16–18 , the outcomes of the carriers were variable, from normal growth to delayed growth 18 . Notably, in cases 21 and 27, pregnancies confirmed with maternal UPD16 were terminated owing to UAs and abnormal genetic results. In our cohort, 62.3% (66/106) of fetuses with LOH presented UAs, and the most common UA was FGR or FGR combined with other indications (18/66 (27.3%)), and the most frequently ultrasound structure anomalies being cardiovascular system malformations (6/66 (9.1%)), skeletal malformations (4/66 (6.1%)), and genitourinary malformations (4/66 (6.1%)). Seventeen percent (18/106) of fetuses with LOH were FGR, UPDs 2, 7, 14, 15, and 16 were the underlying genetic causes of FGR 12,19,20 . The possible pathogenesis encompasses homozygous pathogenic variants in single gene diseases, imprinting effect, or confined placental mosaicism (CPM) 21 . Thus, UPD is one of the possible genetic factors resulting in FGR. Monitoring fetal growth via ultrasound is essential for the management of fetal LOH. Indicative prenatal ultrasound findings can be observed in patients with Beckwith-Wiedemann syndrome and SRS 22,23 . In our cohort, four cases (Cases 6, 25, 26 and 30) with LOH showed FGR or FGR combined with other indications, of which four UPDs were confirmed. The genetic causes underlying FGR were maternal UPD7 and maternal UPD11 associated with SRS 12 , and TOP was elected owing to unfavorable outcomes. Patients with UPD14 showed multiple UAs, resulting in unfavorable outcomes 24,25 . Paternal UPD14 associated with KOS was confirmed in case 4 with polyhydramnios (amniotic fluid index: 38.7 cm), the pregnancy was terminated finally. Notably, the rate of adverse pregnancy outcomes in fetuses with LOH and UAs (36.4%) was higher than in those without UAs (15.0%) ( p < 0.05), our data demonstrate that it is essential that regular ultrasound screening should be examined to closely monitor the development for fetuses with LOH. LOH also provides certain signs for investigating homozygous variants in autosomal recessive single gene diseases besides UPD and imprinting effects. In three cases in our cohort, pathogenic homozygous variants in single gene diseases were further identified via trio-WES, resulting in UAs. Thereby, trio-WES should be first performed for its ability of UPD verification as well as identifying homozygous mutations simultaneously (Cases 11, 16, and 17). Furthermore, six cases (Cases 2, 11, 16, 17, 18, and 29) with clinically significant variant were detected, which were incidental findings. Our study also shows that trio-WES could identify incidental pathogenic mutations in addition to homozygous variants attributed to LOH. Thereby, Trio-WES should be recommended first for fetal LOH, especially in fetuses with structural anomalies and/or consanguineous parents. Our cohort had some limitations. First, although it was a retrospective multicenter study, the sample size was not large enough, studies with larger population will be needed, and the follow-up period was not long enough, which might miss some clinical features. Second, the parental origin of LOH was further identified in only 39.6% of cases and none of the cases were further investigated in placental tissues to confirm CPM. Conclusion We explore the clinical significance and features of fetal LOH. Various molecular genetic testing techniques, such as parental SNP array verification, trio-WES, MS-MLPA, regular and systematic ultrasonic examination, and placental study when necessary, should be comprehensively performed to precisely assess the prognosis of fetal LOH and guide the affected pregnancy management. Declarations Acknowledgments We thank the family members who participated in our study. We also appreciate the obstetricians, radiographers, sonographer and pediatricians who offered assistance to our study. Author contributions HX, LZ and AY prepared the main manuscript; XC, LX, ML, NL, QG, LC, and HH prepared the experiment. All authors have read and approved the final article. Funding This study was sponsored by the Joint Funds for the Innovation of Science and Technology, Fujian Province (no.2020Y9149), 2021 Fujian provincial health technology project (no.2021GGA051), and Natural Science Foundation of Fujian Province (no.2022J01421). Availability of data statement The data used to support the findings of this study are available from the corresponding author upon request. Conflicts of interest The authors confirm that there are no conflicts of interest. Ethics approval and consent to participate The study complied with the principles set forth in the Declaration of Helsinki. It was approved by the Institutional Review Board of Fujian Maternal and Child Health Hospital. Written informed consent was obtained from each patient. Consent for publication Acknowledgements Informed consent was obtained from all patients for being included in the study. Competing interests The authors declare that they have no competing interests. References Levy, B. et al. Genomic imbalance in products of conception: single-nucleotide polymorphism chromosomal microarray analysis. Obstetrics and gynecology 124 , 202-209, doi:10.1097/aog.0000000000000325 (2014). Sahoo, T. et al. Comprehensive genetic analysis of pregnancy loss by chromosomal microarrays: outcomes, benefits, and challenges. Genetics in medicine : official journal of the American College of Medical Genetics 19 , 83-89, doi:10.1038/gim.2016.69 (2017). Del Gaudio, D. et al. Diagnostic testing for uniparental disomy: a points to consider statement from the American College of Medical Genetics and Genomics (ACMG). Genetics in medicine : official journal of the American College of Medical Genetics 22 , 1133-1141, doi:10.1038/s41436-020-0782-9 (2020). Ledbetter, D. H. & Engel, E. Uniparental disomy in humans: development of an imprinting map and its implications for prenatal diagnosis. Human molecular genetics 4 Spec No , 1757-1764, doi:10.1093/hmg/4.suppl_1.1757 (1995). Xue, H. et al. Detection of copy number variation associated with ventriculomegaly in fetuses using single nucleotide polymorphism arrays. Scientific reports 11 , 5291, doi:10.1038/s41598-021-83147-7 (2021). Kearney, H. M., Thorland, E. C., Brown, K. K., Quintero-Rivera, F. & South, S. T. American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. Genetics in medicine : official journal of the American College of Medical Genetics 13 , 680-685, doi:10.1097/GIM.0b013e3182217a3a (2011). Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics (Oxford, England) 25 , 1754-1760, doi:10.1093/bioinformatics/btp324 (2009). Tavtigian, S. V. et al. Modeling the ACMG/AMP variant classification guidelines as a Bayesian classification framework. Genetics in medicine : official journal of the American College of Medical Genetics 20 , 1054-1060, doi:10.1038/gim.2017.210 (2018). Vasconcelos, S., Ramalho, C., Marques, C. J. & Doria, S. Altered expression of epigenetic regulators and imprinted genes in human placenta and fetal tissues from second trimester spontaneous pregnancy losses. Epigenetics 14 , 1234-1244, doi:10.1080/15592294.2019.1634988 (2019). Liu, J. et al. Absence of heterozygosity detected by single-nucleotide polymorphism array in prenatal diagnosis. Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology 57 , 314-323, doi:10.1002/uog.21951 (2021). Hoppman, N., Rumilla, K., Lauer, E., Kearney, H. & Thorland, E. Patterns of homozygosity in patients with uniparental disomy: detection rate and suggested reporting thresholds for SNP microarrays. Genetics in medicine : official journal of the American College of Medical Genetics 20 , 1522-1527, doi:10.1038/gim.2018.24 (2018). Kotzot, D. Prenatal testing for uniparental disomy: indications and clinical relevance. Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology 31 , 100-105, doi:10.1002/uog.5133 (2008). Eggermann, T., Soellner, L., Buiting, K. & Kotzot, D. Mosaicism and uniparental disomy in prenatal diagnosis. Trends in molecular medicine 21 , 77-87, doi:10.1016/j.molmed.2014.11.010 (2015). Robinson, W. P. Mechanisms leading to uniparental disomy and their clinical consequences. BioEssays : news and reviews in molecular, cellular and developmental biology 22 , 452-459, doi:10.1002/(sici)1521-1878(200005)22:53.0.Co;2-k (2000). Liang, B. et al. Prenatal diagnosis of fetuses with region of homozygosity detected by single nucleotide polymorphism array: a retrospective cohort study. Journal of human genetics 67 , 629-638, doi:10.1038/s10038-022-01062-9 (2022). Hansen, W. F. et al. Maternal uniparental disomy of chromosome 2 and confined placental mosaicism for trisomy 2 in a fetus with intrauterine growth restriction, hypospadias, and oligohydramnios. Prenatal diagnosis 17 , 443-450, doi:10.1002/(sici)1097-0223(199705)17:53.0.co;2-2 (1997). Scheuvens, R. et al. Maternal uniparental disomy of chromosome 16 [upd(16)mat]: clinical features are rather caused by (hidden) trisomy 16 mosaicism than by upd(16)mat itself. Clinical genetics 92 , 45-51, doi:10.1111/cge.12958 (2017). Kotzot, D. & Utermann, G. Uniparental disomy (UPD) other than 15: phenotypes and bibliography updated. American journal of medical genetics. Part A 136 , 287-305, doi:10.1002/ajmg.a.30483 (2005). Yingjun, X. et al. Chromosomal uniparental disomy 16 and fetal intrauterine growth restriction. European journal of obstetrics, gynecology, and reproductive biology 211 , 1-7, doi:10.1016/j.ejogrb.2016.12.019 (2017). Carmichael, H., Shen, Y., Nguyen, T. T., Hirschhorn, J. N. & Dauber, A. Whole exome sequencing in a patient with uniparental disomy of chromosome 2 and a complex phenotype. Clinical genetics 84 , 213-222, doi:10.1111/cge.12064 (2013). Wilkins-Haug, L., Quade, B. & Morton, C. C. Confined placental mosaicism as a risk factor among newborns with fetal growth restriction. Prenatal diagnosis 26 , 428-432, doi:10.1002/pd.1430 (2006). Bruce, S. et al. Submicroscopic genomic alterations in Silver-Russell syndrome and Silver-Russell-like patients. Journal of medical genetics 47 , 816-822, doi:10.1136/jmg.2009.069427 (2010). Eggermann, T. et al. Prenatal molecular testing for Beckwith-Wiedemann and Silver-Russell syndromes: a challenge for molecular analysis and genetic counseling. European journal of human genetics : EJHG 24 , 784-793, doi:10.1038/ejhg.2015.224 (2016). Watanabe, T. et al. Prenatal findings and epimutations for paternal uniparental disomy for chromosome 14 syndrome. The journal of obstetrics and gynaecology research 41 , 1133-1136, doi:10.1111/jog.12665 (2015). Chen, C. L. et al. Prenatal diagnosis of paternal uniparental disomy for chromosome 14 using a single-nucleotide-polymorphism-based microarray analysis: A case report. Journal of the Formosan Medical Association = Taiwan yi zhi 118 , 739-742, doi:10.1016/j.jfma.2018.12.010 (2019). Tables Table 1 The detection rate of fatal LOH by SNP array for different invasive testing indications Data are given as n (%). Each case was classified based on most important indication. Classification of indications arranged from most to least important was as follows: ultrasound structural anomalies, fetal karyotype abnormality, soft marker, positive NIPT results, high risk for Down's screening, parental genetic factors, consanguinity, previous adverse pregnancy, AMA and others. * If cases number is less than 20, the percentage is not calculated. # Other ultrasound anomalies included soft-marker anomalies, FGR or fetal overgrowth, hydramnios, hydramnios and abnormal blood flow on doppler ultrasound. LOH, loss of heterozygosity; NIPT, non-invasive prenatal testing; SNP, single nucleotide polymorphism Table 2 Forty-two fetuses with LOH accepted further genetic testing Case GW Prenatal ultrasound findings/Invasive testing indication § Fetal karyotype Fetal LOH region (hg 19) detected by SNP-array Size (Mb) /Percentage (%)* Results of further genetic testing (classification of pathogenicity) Outcome 1 a 22 Oligohydramnios, strephenopodia, consanguineous marriage 46, XX 1p36.33p36.21(888,658-14,505,595) x2 hmz 2q11.1q14.3(95,550,957-127,459,321) x2 hmz 13.6 Mb 31.9 Mb (3.69%) Prenatal trio-WES indicated a homozygous mutation, NM_000302: c.2071_2072 ins CC (p.R693Qfs*122), in PLOD1 (153454) in the fetus, associated with Ehlers-Danlos syndrome type 1 (OMIM 225400) which was located in the LOH of 1p36.33p36.21, and both parents were heterozygous for this variation (LP) Term birth, neonatal death 2 21 Decreased fetal FL/BPD and FL/HC ratio 46, XY 12q23.3q24.32(106,008,417-126,307,790) x2 hmz 20.3 Mb Postnatal trio-WES indicated a heterozygous mutation, NM_001356: c.45+1G>C, in DDX3XP , which is associated with intellectual developmental disorder, X-linked, syndrome, Snijders Blok type (MRXSSB, OMIM:300958) (P) Preterm birth at 36 weeks, BW 2.75 kg diagnosed with hand deformity, autism 3 19+ FGR？intracardiac echogenic focus, increased umbilical artery resistance index, oligohydramnios 46, XX 6p25.3p23(203,878-13,411,320) x2 hmz 6p21.1p11.1(41,305,454-58,726,706) x2 hmz 6q11.1q14.1(61,972,918-75,972,465) x2 hmz 6q22.31q25.1(123,041,062-149,830,858) x2 hmz (containing imprinted genes PLAGL1 (603044) and HYMAI (606546)) 13.2 Mb 17.4 Mb 13.9 Mb 26.7 Mb Prenatal trio-WES indicated mix UPD (6) mat (P) TOP 4 26+3 Polyhydramnios (AFI 38.7 cm) 46, XY arr (14)x2 mos hmz (80%) Mosaicism 80% Parental SNP array verification indicated UPD (14) pat, which is associated with Kagami-Ogata syndrome (P) TOP 5 24 Multiple malformations, thickened prenasal skin, "fish mouth" shape mouth 46, XX 1p36.11p21.2(26,044,678-99,969,487) x2 hmz 3p25.3p14.2(8,746,546-60,897,120) x2 hmz 6p25.1p22.1(5,596,983-28,449,315) x2 hmz 6q24.2q25.2(143,241,806-155,371,652) x2 hmz 7p14.3p11.1(33,991,108-58,019,983) x2 hmz 7q11.21q22.1(62,569,501-98,898,149) x2 hmz 11p15.1p11.12(17,372,347-51,550,787) x2 hmz 11q11q14.1(54,827,207-84,312,637) x2 hmz 73.9 Mb 60 Mb 22.9 Mb 12.1 Mb 22.8 Mb 24 Mb 34.2 Mb 29.5 Mb (10%) Postnatal trio-WES indicated a homozygous mutation, NM_173076.3: c.6577_657 del, in ABCA12 in the fetus, associated with autosomal recessive congenital ichthyosis type 4B type (OMIM 242500) and 4A type (OMIM 601277) (P) Term birth, BW 3.2 kg. The collodion female baby died five days after birth 6 13 +6 FGR 46, XY 7q31.31q36.3(120138084_159118443) x2 hmz 39 Mb Parental SNP array verification indicated UPD (7) mat, which is associated with Silver-Russell syndrome (P) TOP 7 18 + AMA 46, XX 2q22.3q31.1(144,624,648-173,171,481) x2 hmz 4q13.1q21.3(63,730,113-87,252,596) x2 hmz 28.5 Mb 23.5 Mb Prenatal trio-WES indicated no clinically relevant mutations. Term birth (Normal phenotype) 8 23 + Small fetal BPD and HC for gestation age 46, XX 14q32.11q32.31(91556694_101593701) x2 hmz 10 Mb Prenatal trio-WES indicated no clinically relevant mutations. Term birth (Normal phenotype) 9 24 Fetal ARSA 46, XY 1p36.21p35.2(15,728,288-31,781,279) x2 hmz 4p15.2p11(25,981,952-49,063,479) x2 hmz 16 Mb 23 Mb Prenatal trio-WES indicated no clinically relevant mutations., and identified a homozygous mutation, NM_015378: c.427A>G (p.R143G), in VPS13D in the fetus, associated with autosomal recessive spinocerebellar, ataxia, autosomal recessive 4 (SCAR4, OMIM 607317) (VOUS) Term birth (Normal phenotype) 10 25 Fetal bilateral renal enlargement, increased renal echogenicity 46, XY 8q11.23q24.3(55365228_146292734) x2 hmz 90.9 Mb Prenatal trio-WES indicated UPD (8q11.23-q24.3) mat (VOUS) Term birth (Normal phenotype) 11 26 Small fetal BPD was small for gestation age, consanguineous marriage 46, XX 14q13.1q24.2(34435418_72618432) x2 hmz 38 Mb Postnatal trio-WES confirmed no indication of UPD (14), and showed a heterozygous mutation, NM _000095: c.1417_1419 dup (p.D473dup), in COMP in the female infant, associated with autosomal dominant pesudoachondroplasia, (PSACH, OMIM177170), epiphyseal dysplasia, multiple, 1 (EDM1,OMIM 132400), and carpal tunnel syndrome 2 (CTS2, OMIM 619161) (LP) Term birth Now the infant is 5 months old, 60 cm tall, and often arches her back, Brain MRI revealed that bilateral ventricles were asymmetrical, and the left lateral ventricle was larger than the right. Some of the extracerebral spaces are slightly widened. Low T1W1 and high T2W1 signals were observed in bilateral maxillary sinus, ethmoid sinus and sphenoid sinus. 12 22 FGR; high risk of trisomy 15 detected by NIPT; AMA 46, XY 15q21.3q26.1(53188649_90583138) x2 hmz 37.4 Mb Prenatal trio-WES indicated mixed UPD (15q21.3q26.1) mat associated with PWS (P) TOP 13 18 Thickened nuchal translucency (2.8 mm), cervical lymphatic hygroma 46, XX 6p12.2p11.1(52607147_58726706) x2 hmz, 6q11.1q12(60972918_66615551) x2 hmz 6.1 Mb 5.6 Mb Prenatal trio-WES indicated no clinically relevant mutations. TOP 14 25 Fetal RAA-ARSA 46, XY 7q21.13q36.3(88,712,610-159,118,443) x2 mos hmz (45%) 70.4 Mb First, parental SNP array verification indicated it is not possible to determine whether the LOH of chromosome 7 is paternal or maternal; Then, MS-MLPA for the methylation analysis of 7q21.13q36.1 loci, MS-MLPA revealed that the relative copy numbers of the three methylation probes (184 bp, 190 bp, and 256 bp) in MEST gene (maternal methylation gene region, paternal methylation was preferentially expressed) were 0.66, 0.66 and 0.64, respectively, suggesting a possible low proportion mosaic UPD (7) mat. However, the experimental results are near the threshold range, so it cannot be interpreted accurately (P) Term birth Feeding difficulties exist after birth, now 3 months after delivery, the child's height and development is normal, only light weight 15 23+ Fetal bilateral renal enlargement, increased renal echogenicity 46, XX 6p12.3q14.1(46587519_77260358) x2 hmz 27.45 Mb (0.95%) Prenatal trio-WES revealed a homozygous mutation, NM_138694.4: c.1233G>A p.K411K, in PKHD1 in the fetus, associated with autosomal recessive polysystic kidney disease 4, with or without hepatic Disease (OMIM 263200) (P) TOP 16 21+ Reproductive history of children with chromosomal abnormalities (arr[hg19]9p24.3p22.3(203861_16540793) x1, 9p22.3p13.3(16540940_34942483) x3, which is associated with 9p partial monosomy syndrome and 9p trisomy, respectively; AMA 46, XY 18p11.32p11.21(136305_15079294) x2 hmz 18q11.1q23(18552517_77997606) x2 hmz 15 Mb 59 Mb Prenatal trio-WES indicated UPD(18) pat, and also revealed a heterozygous splicing mutation, NM_006767.4: c.2069+1G>A, in LZTR1 in the fetus, associated with noonan syndrome 2 (NS10, OMIM 616564）and schwannomatosis-1, susceptibility, (OMIM 615670), inherited paternally (LP) CTP 17 18+ NIPT indicated a 8.2 Mb deletion at 4q31-qter (FF: 6.4 %) 46, XY 4q32.3q35.2(167230247_190921709) x2 hmz 23.7 Mb Trio-WES indicated iso UPD (4q32.3q35.2) mat [(UPD (4)], and also revealed a heterozygous splicing mutation, NM_001807.6, in CEL in the fetus, associated with maturity-onset diabetes of the young, type VIII (OMIM 609812), inherited paternally (LP) Term birth, Currently developing normally at 2 years old 18 20 Lethal bone dysplasia (osteogenesis imperfecta type II) 46, XX 5q23.2q32(125,771,613-145,714,232) x2 hmz 20 Mb Prenatal trio-WES indicated a de novo missense variant, NM_000088: c.1436G>C p.G479A, in COL1A1 (120150) on chromosome 17, associated with osteogenesis imperfecta, type I (OMIM166200), type II (OMIM 166210), type III (OMIM 259420), type IV (OMIM 166220), Ehlers-Danlos syndrome, arthrochalasia type 1 (OMIM 130060), Caffey disease (OMIM 114000), and bone mineral density variation QTL, steoporosis (OMIM 166710) (P) TOP 19 28+ FGR 46, XX 15q14q21.3(35,077,111-54,347,324) x2 hmz 19.2 Mb Parental SNP array verification indicated UPD (15) mat, associated with PWS (P) TOP 20 27+ Narrow inner diameter of aortic arch, increased renal echogenicity, FGR, persistent left superior vena cava, thickening of the placenta 46, XY 2p25.3p11.2(50,813-87,053,152) x2 hmz 2q11.1q37.3(95,550,957-242,773,583) x2 hmz 82.0 Mb 147.2 Mb Parental SNP array verification indicated UPD (2) mat (VOUS) TOP 21 23+ VSD, FGR, aortic stenosis, left kidney dysplasia or absence, enhanced intestinal echo 46, XX 16q23.2q24.3(79,800,878-90,146,366) x2 hmz 16p13.3p12.3(94,807-19,302,326) x2 hmz 10.3Mb 19.2Mb Parental SNP array verification indicated UPD (16) mat (P) TOP 22 22+ FGR, mild tricuspid regurgitation, reverse a-wave of ductus venosus, enhanced intestinal echo 46, XY 6p25.3q27(203,877-170,896,644) x2 hmz 170.7 Mb Parental SNP array verification indicated UPD (6) pat, associated with transient neonatal diabetes (P) TOP 23 19 Amniocentesis: 47, XX, +mar dn; high risk of trisomy18 screening 47, XX, +mar dn 3p13p12.1(72,069,483-86,073,653) x2 hmz 3q11.2q22.3(95,320,713-137,634,506) x2 hmz 14.0 Mb 42.3 Mb Parental SNP array verification indicated UPD (3) mat (VOUS) Term birth, currently developing normally at 1.5 years old 24 29 Sever FGR 46, XX 15q11.2q22.2(22,817,870-62,568,746) x2 hmz 15q26.2q26.3(96,143,558-102,397,317) x2 hmz 39.7 Mb 6.25 Mb Parental SNP array verification indicated UPD (15) mat, associated with PWS (P) TOP 25 FGR, high risk of trisomy 21 screening 46, XY 11p15.5p15.4(205,827-8,150,933) x2 hmz 8 Mb Parental SNP array verification indicated UPD (11) mat, associated with Silver-Russell syndrome (P) TOP 26 30 Severe FGR 46, XX 7p22.3p12.2(50944_157155880) x2 hmz 50.4 Mb Parental SNP array verification indicated UPD (7p22.3p12.2) mat, associated with Silver-Russell syndrome (P) TOP 27 23 Fetal HC was less than the mean 3SD; high risk of trisomy 16 detected by NIPT (Z=18.705) 46, XX 16q22.3q24.3(73705779_90146366) x2 hmz 16 Mb Parental SNP array verification indicated mixed UPD (16) mat (VOUS) TOP 28 25 FGR; high risk of trisomy 16 detected by NIPT (Z=25.2); AMA, 46, XY 6p25.3q27(203,877-170,896,644) x2 hmz 170.7 Mb Parental SNP array verification indicated mixed UPD (6) mat (VOUS) TOP 29 23 Fetal bilateral femoral curvature, less than the normal predictive value -2SD 46, XY 5p15.33p11(113,576-46,242,541) x2 hmz 46.1 Mb Prenatal trio-WES indicated an inherited paternally splicing variant, NM_000088.4: c.1615-1G>T (p. G802V), in COL1A1 (120150) on chromosome 17, associated with autosomal dominant osteogenesis imperfecta (P) TOP 30 29 Hydrops fetalis, FGR 46, X, i(Xq) [40]/45, X[14] 11p15.5p15.4(230,750-8,050,928) x2 hmz 7 Mb Parental SNP array verification indicated UPD (11) mat, associated with Silver-Russell syndrome (P) TOP 31 26 FGR, high risk of trisomy 21 screening 46, XX 7q11.21q11.23(62569502_75233244) x2 hmz 7p14.1p11.1(42421781_58019983) x2 hmz 9q21.13q22.2(78780578_92509057) x2 hmz 12.7 Mb 15.6 Mb 13,7 Mb Prenatal trio-WES indicated no clinically relevant mutations. Term birth, currently developing normally at 2 years old 32 18 High risk of trisomy 21 screening 46, XY 7q22.3q31.32(107306055_122301501) x2 hmz 15 Mb Prenatal trio-WES indicated no clinically relevant mutations. Term birth, Currently developing normally at 2.5years old.. 33 19 Deep notch a-wave of ductus venosus 46, XX 13q14.2q21.2(47358540_61986828) x2 hmz 14.6 Mb Prenatal trio-WES indicated no clinically relevant mutations. Term birth, Currently developing normally at 2 years old.. 34 25 Fetal micrognathia, small BPD, HC and FL for gestation age 46, XY 5q15q22.1(94849287_110237725) x2 hmz 15.39 Mb Prenatal trio-WES indicated no clinically relevant mutations. Term birth, micrognathia 35 23 Fetal suprachivalal stenosis 46, XX 1p31.3p31.1(65532190_78558941) x2 hmz 13.03 Mb Prenatal trio-WES indicated no clinically relevant mutations. Term birth, normal development 36 22 Fetal pulmonary sequestration 46, XX 2p24.3p21(16,435,384-42,306,722) x2 hmz 25.8 Mb Parental SNP array verification indicated IBD Term birth, normal development 37 18 Thickened nuchal translucency (3.5 mm); AMA 46, XY 14q11.2q12(22,094,953-32,626,332) x2 hmz 10.5 Mb Parental SNP array verification indicated IBD Term birth, normal development 38 19 Pregnant women had a child with mental retardation; AMA 46, XX 3p22.1p14.2(42390369_60178833) x2 hmz 17.7 Mb Parental SNP array verification indicated IBD Term birth, normal development 39 18 Previous adverse pregnancy 46, XY 15q21.2q22.2(49971494_63093257) x2 hmz 13.1 Mb Parental SNP array verification indicated IBD Term birth, normal development 40 18+ FGR, previous adverse pregnancy 46, XY 6p21.31p11.1(33808094_58726706) x2 hmz, 6q11.1q16.1(61972918_93717031) x2 hmz 24.9 Mb 31.7 Mb Parental SNP array verification indicated IBD Term birth, normal development 41 19 AMA 46, XX 6q14.3q21(87,299,268-110,741,585) x2 hmz 23.4 Mb Parental SNP array verification indicated IBD Term birth, normal development 42 20 Thickened nuchal translucency (3.0 mm); AMA 46, XX 1q21.1q21.2(144,077,593-148,750,533) x2 hmz 3p21.31p21.1(48,166,782-53,172,233) x2 hmz 5q21.3q22.1(107,196,975-110,478,806) x2 hmz 12q21.31q21.33(82,446,525-91,707,400) x2 hmz 14q31.2q32.12(84,339,970-92,755,472) x2 hmz 15q24.1q25.3(73,065,223-87,467,262) x2 hmz 16p13.3(94,807-3,112,982) x2 hmz 17p12p11.2(15,838,698-22,170,994) x2 hmz 54.2 Mb (2%) Parental SNP array verification indicated IBD Term birth, normal development *The percentage is calculated by the sum of the size (Mb) of the LOH segments over 5 Mb divided by ~2781 Mb. § Each case was classified based on its most important invasive diagnostic indication. The classification of indications, arranged in the order of importance are as follows: ultrasound anomalies, positive NIPT results, high risk for Down’ screening, parental abnormal karyotype, consanguinity, previous adverse pregnancies, AMA, suspected fetal infection, and others. AMA, advanced maternal age; AFI, amniotic fluid index; ARSA, aberrant left subclavian artery; BW, birth weight; BPD, biparietal diameter; FL, femur length; FGR fetal growth restriction; GW, gestational weeks; HC, head circumference; IBD, identity by descent; LOH, loss of heterozygosity; LP, likely pathogenic; Mat, maternal; MS-MLPA, methylation-specific multiplex ligation-dependent probe amplification; NIPT, noninvasive prenatal testing; OMIM, online mendelian inheritance in man; Pat, paternal; P, pathogenic; PWS, prader-willi syndrome; RAA, right aortic arch; SNP, single nucleotide polymorphism; TOP, terminal of pregnancy; UPD, uniparental disomy; VSD, ventricular septal defect Table 3 The detailed 64 prenatally diagnosed fetuses with LOH declined parental SNP array verification or further genetic testing Case GW Prenatal imaging findings/Invasive testing indication Fetal karyotype Fetal LOH region detected by SNP-array results [hg19] Size (Mb) /Percentage (%)* Outcome 43 18+ Her husband carries 46, XY, t(4;5)(q31;q23), consanguineous marriage 46, XX, t (4;5) (q31; q23) pat 18p11.32p11.21(136,304-15,079,294) x2 hmz 15 Mb Term birth, normal development 44 25 FGR, enhanced intestinal echo 46, XX 8p23.1p21.3(8117565_21609098) x2 hmz 13.5 Mb Term birth, normal development 45 23+ Small femur length for gestation age; high risk of trisomy 22 detected by NIPT 46, XY 22q12.3q13.33(35,156,334-51,157,531) x2 hmz 16 Mb Term birth, normal development 46 20 Del (8p) detected by NIPT; AMA 46, XY 8p23.3p23.1(168,483-6,999,220) x2 hmz, 8p23.1p12(8,117,564-32,069,805) x2 hmz 6.8 Mb 23.9 Mb Term birth, normal development 47 18+ Consanguineous marriage; pregnant women had a child with mental retardation 46, XX 8p23.3p23.1(2,142,556-6,999,220) x2 hmz 67.9 Mb (3.63%) Term birth Mental retardation 48 21 Enhanced intestinal echo; Pregnant women had three children with cardiac malformation 46, XX 13q14.2q22.3(49,157,476-78,073,267) x2 hmz 29 Mb Term birth, normal development 49 12 Fetal cystic hygroma 46, XY 9q21.13q21.33(77,263,747-89,236,178) x2 hmz 9q22.33q31.1(101,366,537-107,749,439) x2 hmz 10q22.3q24.1(80,035,256-97,660,572) x2 hmz 14q31.1q32.2(79,435,542-97,071,550) x2 hmz 17q24.2q25.3(67,002,309-81,041,760) x2 hmz 18q22.3q23(71,555,375-77,997,606) x2 hmz 19q12q13.33(31,360,714-49,513,502) x2 hmz 21q21.1q22.13(19,573,963-39,057,622) x2 hmz 111.74 Mb (4.02%) Missed abortion 50 14+ AMA 46, XY 9q22.33q33.1(101944435_121284276) x2 hmz 19.3 Mb Missed abortion 51 20 Coarctation of the fetal aorta 46, XX 19p13.2p11(6939202_24462369) x2 hmz 17.5 Mb Intrauterine demise 52 15 Hydrops fetalis 46, XY 5q11.1q35.3(49564628_180692321) x2 mos hmz (30%) 130 Mb Missed abortion 53 16 Fetal giant bladder 46, XX 5q34q35.3(164130490_176629546) x2 hmz 12.5 Mb Missed abortion 54 25 Fetal dysplasia or absence of left radius, abnormal left lower limb posture, single umbilical artery 46, XY 16q22.3q24.3(73294159_90146366) x2 hmz 16.8 Mb TOP 55 15 Thickened NT (5 mm) 46, XX 3p14.2p11.1(59365038_90485635) x2 hmz 3q11.1q13.11(93558926_103243507) x2 hmz 31 Mb 10 Mb Missed abortion 56 23 Small femur length and humerus length for gestation age 46, XX 4q28.3q31.3(133,718,289-154,569,367) x2 hmz 20.8 Mb Term birth, normal development 57 26+ Fetal ventriculomegaly (1.4 cm), large for gestational age 46, XY 3q26.1q29(163,256,369-197,791,601) x2 hmz 5p13.1p11(41,029,137-46,313,469) x2 hmz 6q24.2q26(143,341,406-161,527,784) x2 hmz 12q13.2q21.2(56,011,100-77,134,151) x2 hmz 17q21.2q21.32(39,639,602-45,479,706) x2 hmz 21q21.3q22.2(28,124,165-42,352,287) x2 hmz 99.1Mb (3.57%) TOP 58 24 Fetal infantile polycystic kidney disease? 46, XX 2q31.1q35(175,428,638-216,907,322) x2 hmz, 5q14.3q22.3(85,447,858-113,850,052) x2 hmz 41 Mb 28 Mb TOP 59 28+ FGR, small fetal HC for gestation age 46, XY 5q15q22.2(94637916_112744413) x2 hmz 18.1 Mb Preterm birth 60 19 AMA 46, XY 10q23.1q25.1(86,546,612-109,956,967) x2 hmz 23.4 Mb Term birth, normal development 61 25 Fetal tetralogy of Fallot, thickened NT (4.7 mm) 46, XY 1p33p32.3(50,051,514-53,274,566) x2 hmz 2q23.3q24.1(153,771,280-158,783,675) x2 hmz 3q21.2q22.1(124,817,983-129,317,745) x2 hmz 3q22.1q23(133,262,566-139,418,898) x2 hmz 3q26.1q26.2(161,540,639-168,592,236) x2 hmz 7p22.3p21.2(2,707,568-13,857,235) x2 hmz 8q23.3q24.12(114,788,423-119,897,611) x2 hmz 9p22.1p13.3(19,696,747-36,125,149) x2 hmz 11q12.2q12.3(60,193,879-63,210,491) x2 hmz 11p11.2p11.12(45,781,075-51,550,787) x2 hmz 17q21.31q21.32(41,647,165-44,927,874) x2 hmz 17q25.1q25.3(71,965,953-75,785,426) x2 hmz 20p11.23p11.21(20,268,153-23,275,237) x2 hmz 77.5 Mb (2.8%) TOP 62 23+ Amniocentesis: 46,XY,t(11;22)(q24.1;q12.3) dn; AMA 46, XY, t (11;22) (q24.1; q12.3) dn 3p13q13.31(71,435,373-116,447,779) x2 hmz 45.0 Mb Term birth, normal development 63 22 Fetal diaphragmatic hernia, permanent right umbilical vein, high risk of trisomy 21 screening 46, XY 22q11.1q13.32(16,888,899-48,538,372) x2 hmz 31.6 Mb TOP 64 19+ High risk of trisomy 21 screening, consanguineous marriage 46, XX 8q23.1q23.3(109,495,878-115,007,395) x2 hmz 8q24.21q24.3(128,517,572-143,689,390) x2 hmz 10q24.2q25.1(101,324,364-109,677,582) x2 hmz 11q24.2q25(123,916,776-132,360,867) x2 hmz 16q11.2q12.2(46,504,466-55,451,871) x2 hmz 19q13.12q13.32(36,345,999-45,532,009) x2 hmz 46.4 Mb (2.89%) Term birth, normal development 65 18 Adverse pregnancy history 46, XY 3p26.1p24.1(8,494,626-26,413,121) x2 hmz 17.9 Mb Term birth, normal development 66 18+ High risk of trisomy 21 screening 46, XX 4q32.1q34.3(161,662,054-181,126,952) x2 hmz 19.5 Mb Term birth, normal development 67 19+ AMA, RSA 46, XY 15q21.1q24.2(49,174,353-76,415,329) x2 hmz 27.2 Mb Term birth, normal development 68 30= Fetal ventriculomegaly (1.4 cm) 46, XX 1q25.2q31.3(179,562,791-198,041,374) x2 hmz 1p33p32.3(49,189,774-53,588,443) x2 hmz 1p31.1p22.1(83,490,160-94,219,311) x2 hmz 3q22.2q22.3(135,242,870-138,329,862) x2 hmz 3p14.1p13(65,159,530-71,254,193) x2 hmz 3q12.1q12.3(99,386,363-102,630,046) x2 hmz 4q34.3q35.1(178,198,740-183,532,267) x2 hmz 5q33.3q34(157,473,329-162,124,378) x2 hmz 8p21.2p12(25,313,218-29,802,727) x2 hmz 9q22.1q31.2(90,844,062-108,221,369) x2 hmz 10q21.1q22.1(54,568,807-72,273,380) x2 hmz 11p11.2p11.12(45,959,522-51,550,787) x2 hmz 13q31.3q32.3(93,816,292-101,526,284) x2 hmz 18q11.1q11.2(18,552,516-23,353,126) x2 hmz 18p11.31p11.21(4,951,983-15,079,294) x2 hmz 20p13p12.3(61,794-5,436,062) x2 hmz 129.19 Mb (4.65%) Term birth, hydrocephalus, abnormal fingers on both hands, learning disability 69 23 Fetal cleft palate 46, XY 8q24.22q24.3(134,714,740-146,292,734) x2 hmz 11.6 Mb TOP 70 18+ AMA 46, XX 10q24.32q25.3(104,021,108-115,579,812) x2 hmz 11.5 Mb Term birth, normal development 71 19+ AMA 46, XY 1p36.12p34.2(22,992,252-40,994,050) x2 hmz 18 Mb Term birth, normal development 72 23+ Hydramnios, AMA 46, XX 2q31.1q32.2(177,156,393-190,026,211) x2 hmz 12.8 Mb Preterm birth, normal development 73 20+ High risk of trisomy 21 screening 46, XX 15q14q21.1(37,475,111-48,299,651) x2 hmz 10.8 Mb Term birth, normal development 74 22+ Hyperechoic nodules in fetal liver 46, XX 2q11.1q12.3(95,550,957-108,770,463) x2 hmz 13.2 Mb Term birth, normal development 75 20 AMA, embryo arrest in one of the twin pregnancy 46, XY 5q11.1q13.2(49560858_68826246) x2 hmz 5p13.2p11(38119461_46383335) x2 hmz 10q11.22q21.1(48654362_59013629) x2 hmz 14q32.2q32.33(98824485_107285437) x2 hmz 17q11.1q11.2(25309336_30880382) x2 hmz 17p12p11.1(13895964_22217883) x2 hmz 19.26 Mb 8.26 Mb 10.36 Mb 8.46 Mb 5.57 Mb 8.32 Mb Term birth, normal development 76 18+ AMA 46, XY 10q22.3q23.33(79424943_95211586) x2 hmz 15.79 Mb Term birth, normal development 77 27 Small fetal BPD for gestation age, mild tricuspid regurgitation 46, XX 6q22.31q23.3(124043730_137024585) x2 hmz 12.98 Mb Term birth, normal development 78 19 AMA 47, XX, +21 arr (21)x3 18p11.32p11.21(136,304-15,079,294) x2 hmz 14.9 Mb TOP 79 21+ Thickened NT (4.7 mm) 46, XY 3p12.3p11.1(78796314_90485635) x2 hmz 11.7 Mb Term birth, normal development 80 19+ Pregnant women with mental retardation, night blindness, consanguineous marriage 46, XY 13q13.3q21.33(38088920_71004437) x2 hmz 32.9 Mb Term birth, normal development 81 25+ Fetal lung cystic adenoma 5q31.3q34(141922621_162299719) x2 hmz 20 Mb TOP 82 22 Fetal enhanced intestinal echo 46, XX 1q32.2q44(208165416_245084139) x2 hmz 36.9 Mb Term birth, normal development 83 18+ High risk of trisomy 1 and trisomy 8 detected by NIPT 46, XY 10q23.1q25.1(87343533_109730397) x2 hmz 22.4 Mb Term birth, normal development 84 26 Fetal slightly thickened pulmonary valve, strephenopodia, pulmonary valve and tricuspid valve mild regurgitation 46, XY 3p26.2p25.1(2886527_13828221) x2 hmz 4p16.3p15.33(3473602_14373371) x2 hmz 5p13.3p11(31554333_46313469) x2 hmz 10.9 Mb 10.9 Mb 14.8 Mb TOP 85 19 Absent fetal nasal bone, high risk of trisomy 18 46, XX 2p16.1p13.2(55018895_72337985) x2 hmz 2q11.2q31.1(101324333_177929684) x2 hmz 3q13.33q21.3(119592046_128125154) x2 hmz 4q34.3q35.2(181657468_190921709) x2 hmz 4q26q31.21(116436130_145124024) x2 hmz 5q23.3q33.3(128032159_157973399) x2 hmz 11q11q13.3(54827208_69837254) x2 hmz 11p14.3p11.12(21783630_51550787) x2 hmz 12q12q24.31(46091467_124915560) x2 hmz 15q22.31q24.1(66572692_73290903) x2 hmz 17p13.3p13.1(1365961_8388179) x2 hmz 17q22q24.1(55220296_64161582) x2 hmz 17q24.3q25.3(69423334_81041760) x2 hmz 21q22.12q22.3(36678533_48061211) x2 hmz 339.6 Mb (12.2%) Term birth, normal development 86 18 hypoplastic nasal bone, high risk of trisomy 21 detected by NIPT 46, XY 3q12.1q13.2(99160747_111326722) x2 hmz 12.2 Mb Term birth, normal development 87 18+ The husband of the pregnant woman carries 46,XY, t(2;6)(p21;q21) 46, XX 11p15.5p15.4(230751_5408252) x2 hmz 5.18 Mb Term birth, normal development 88 30 FGR 46, XY 3q11.2q13.13(97766775_109823273) x2 hmz 4q27q32.1(121203882_156320512) x2 hmz 12 Mb 35 Mb Preterm birth, normal development 89 19+ Deletion in 1p36.3 detected by NIPT, AMA 46, XX 1p36.33p36.13(888659_18328851) x2 hmz 17.4 Mb Term birth 90 20 Thickened NT (3.2 mm) 46, XY 2q24.3q31.1(164542492_174491805) x2 hmz 10 Mb Term birth, normal development 91 25+ Fetal portal-body venous shunt outside the liver 46, XY 4p15.2p11(22224153_49063479) x2 hmz 26.8 Mb Term birth, normal development 92 19+ High risk of trisomy 21 screening 46, XX 8q13.3q21.13(72567811_83036411) x2 hmz 10.5 Mb Term birth, normal development 93 18+ Deep notch a-wave of ductus venosus, adverse pregnancy history 46, XY 13q14.2q21.2(47320304_61602456) x2 hmz 14.3 Mb Term birth, normal development 94 18 Adverse pregnancy history 46, XY 2q11.1q11.2(95550958_100799003) x2 hmz 9p24.1p13.2(8235898_36732597) x2 hmz 18q11.2q22.1(23795473_66441448) x2 hmz 20q13.12q13.32(43817586_56736674) x2 hmz 89.3 Mb (3.21%) Term birth, normal development 95 18+ High risk of trisomy 21 screening 46, XY 18q12.2q21.1(35074699_45621145) x2 hmz 10.55 Mb Term birth, normal development 96 26 Fetal right ventricle is slightly smaller than the left ventricle, slightly smaller the inner diameter of the pulmonary artery and left and right pulmonary artery, and mild tricuspid regurgitation, high risk of trisomy 21 screening mos 47, XY, +22[3]/46, XY [58] arr (22)x2.3 (30% mos) 22q12.3q13.33(36679058_51157531) x2 hmz 14.5 Mb TOP 97 19+ High risk of fetal sex chromosome aneuploidy detected by NIPT, AMA 46, XX 3q13.13q22.2(110489883_134438659) x2 hmz 23.9 Mb Term birth, normal development 98 20 Fetal bilateral choroid plexus cysts, intracardiac echogenic focus, high risk of fetal sex chromosome aneuploidy detected by NIPT 46, XY 3p13p11.1(72195690_90485635) x2 hmz 3q11.1q12.2(93558926_100589330) x2 hmz 4q31.21q32.3(145585354_165933062) x2 hmz 6q26q27(161702754_170896644) x2 hmz 11p13p11.12(36146925_51550787) x2 hmz 11q11q12.2(54827208_60193880) x2 hmz 75.6 Mb (2.72%) Term birth, normal development 99 19+ The pregnant woman carries 46, XX, t(12;21)(q12;q22) 46, XX, t (12;21) (q12; q22.2) mat 3p12.3q12.2(78304909_100613493) x2 hmz 22 Mb Term birth, normal development 100 20+ Fetal separation of right renal pelvis, intracardiac echogenic focus 46, XY 14q23.2q24.3(62101707_77219310) x2 hmz 15 Mb Term birth, normal development 101 28 Fetal multiple calcification foci in fetal abdominal cavity 46, XY 2q24.1q24.3(156,461,811-165,665,567) x2 hmz 2p13.2p11.2(72,170,192-83,714,557) x2 hmz 9.2 Mb 20.7 Mb Term birth, normal development 102 31 Fetal agenesis of the corpus callosum 46, XX 13q21.2q31.1(61,365,983-85,033,012) x2 hmz 23 Mb TOP 103 25 FGR 46, XX 6q12q14.1(69812646_82725168) x2 hmz 12.9 Mb Preterm birth, normal development 104 30+ FGR, amniocentesis: 47,XN,+mar[57]/46,XN[41] 47, XN, +mar [57]/46, XN [41] dn 6p12.3q13(47138118_74152240) x2.77 6p25.3p12.3(203877_47207081) x2 hmz 6q13q27(74056154_170896644) x2 hmz 27.0 Mb 96.8 Mb TOP 105 29+ FGR, increased intestinal echo 46, XY 12p13.2p12.1(10143600_22685434) x2 hmz 12.5 Mb Term birth, normal development 106 21 AMA 46, X, inv(Y) (p11.2q11.2) mos 45% arr (13)x2 mos hmz (45%) Term birth, epilepsy, mild mental retardation *The percentage is calculated by the sum of the size (Mb) of the LOH segments over 5 Mb divided by ~2781 Mb. § Each case was classified based on its most important invasive diagnostic indication. The classification of indications, arranged in the order of importance are as follows: ultrasound anomalies, positive NIPT results, high risk for Down’ screening, parental abnormal karyotype, consanguinity, previous adverse pregnancies, AMA, suspected fetal infection, and others. AMA, advanced maternal age; BPD, biparietal diameter; dn, de novo; FGR, fetal growth restriction; hmz, homozygosity; NIPT, noninvasive prenatal testing; NT, nuchal translucency; RSA, recurrent spontaneous abortion; SNP, single nucleotide polymorphism; TOP, termination of pregnancy. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 25 Jan, 2024 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Major revision 25 Oct, 2023 Reviews received at journal 28 Sep, 2023 Reviewers agreed at journal 12 Sep, 2023 Reviews received at journal 09 Sep, 2023 Reviewers agreed at journal 01 Sep, 2023 Reviewers invited by journal 02 Aug, 2023 Editor assigned by journal 01 Aug, 2023 Editor invited by journal 27 Jul, 2023 Submission checks completed at journal 27 Jul, 2023 First submitted to journal 03 Jul, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3137002","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":222095370,"identity":"d0ecde9f-9a67-4f63-9052-ec465df05344","order_by":0,"name":"Huili Xue","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxUlEQVRIiWNgGAWjYDACCQaGAw8Mapjt2xsbH34gWkuCwTF2A57DzcYSxGphSGBg5jeQSG8T4CFGh8HtHsMDCQVs0uaSD9uA+u3kdBsIaJGcc8YA6DAZY8vZiW0PChiSjc0OENDCL5ED0sKWzHA7sd1AguFA4jZCWtggWpjrG24ebJPgIUYL1BZmZoMbjERqkZyRVgAKZGbJnkRgIBsQ4ReDG8mbP3z4U8PMz3784cMPFXZyBLWgm0Ca8lEwCkbBKBgFOAAACBxBsMV+TKUAAAAASUVORK5CYII=","orcid":"","institution":"Fujian Medical University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Huili","middleName":"","lastName":"Xue","suffix":""},{"id":222095371,"identity":"bc09b136-684b-4d9e-9a4a-fbc21e994081","order_by":1,"name":"Aili Yu","email":"","orcid":"","institution":"Fujian Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Aili","middleName":"","lastName":"Yu","suffix":""},{"id":222095372,"identity":"a2683ff1-0b5f-467f-b3a5-bd2e7ab4a948","order_by":2,"name":"Lin Zhang","email":"","orcid":"","institution":"Fujian Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Lin","middleName":"","lastName":"Zhang","suffix":""},{"id":222095373,"identity":"f8711351-daca-44e5-a634-da4c96450a0d","order_by":3,"name":"Lingji Chen","email":"","orcid":"","institution":"Fujian Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Lingji","middleName":"","lastName":"Chen","suffix":""},{"id":222095374,"identity":"979ba981-72b0-4c78-99b2-64a7ff76852e","order_by":4,"name":"Qun Guo","email":"","orcid":"","institution":"Fujian Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Qun","middleName":"","lastName":"Guo","suffix":""},{"id":222095375,"identity":"bd849fcd-1acc-4f71-ad45-708b7a6b8761","order_by":5,"name":"Min Lin","email":"","orcid":"","institution":"Fujian Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Min","middleName":"","lastName":"Lin","suffix":""},{"id":222095376,"identity":"1effa3b4-dd95-4a1c-a8d5-95c7104688ce","order_by":6,"name":"Na lin","email":"","orcid":"","institution":"Fujian Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Na","middleName":"","lastName":"lin","suffix":""},{"id":222095377,"identity":"9d33cb84-9fa5-4cd7-b133-7e0b13c6de24","order_by":7,"name":"Xuemei Chen","email":"","orcid":"","institution":"Fujian Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xuemei","middleName":"","lastName":"Chen","suffix":""},{"id":222095378,"identity":"a6905261-325f-4f64-bb54-475fc0394c61","order_by":8,"name":"Liangpu Xu","email":"","orcid":"","institution":"Fujian Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Liangpu","middleName":"","lastName":"Xu","suffix":""},{"id":222095379,"identity":"ba9d4682-6f18-4486-aea1-4d6f7ecc00f5","order_by":9,"name":"Hailong Huang","email":"","orcid":"","institution":"Fujian Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hailong","middleName":"","lastName":"Huang","suffix":""}],"badges":[],"createdAt":"2023-07-03 22:29:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3137002/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3137002/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-024-52812-y","type":"published","date":"2024-01-25T15:13:10+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":40913479,"identity":"7f9f1d4c-c80d-4558-94d7-5275c97d5b94","added_by":"auto","created_at":"2023-08-01 22:54:10","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":64164,"visible":true,"origin":"","legend":"\u003cp\u003eThe flow chart of fetal LOH analysis in our cohort.\u003c/p\u003e\n\u003cp\u003eIBD, identity by descent; LOH, loss of heterozygosity; SNP array, single nucleotide polymorphism array; UPD, uniparental disomy; VOUS, variant of unknown significance; WES, whole exome sequencing.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3137002/v1/8359abb6e308c349465c0e33.png"},{"id":40911462,"identity":"ac1e3f15-5575-4f08-804f-0f5bcc127625","added_by":"auto","created_at":"2023-08-01 22:46:10","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1432065,"visible":true,"origin":"","legend":"\u003cp\u003eA 70.4 Mb loss of heterozygosity (LOH) was detected by SNP array (A), and further confirmed as maternal uniparental disomy 7 (UPD7) (B and C) for case 14.\u003c/p\u003e\n\u003cp\u003eDetection of a 70.4 Mb segmental LOH on 7q21.13q36.3 using a SNP array. Purple bars represent stretches of LOH occurring on 7q21.13q36.3. The allele difference panel indicates the genotype for each SNP.\u003c/p\u003e\n\u003cp\u003eConfirmation of low proportion mosaic maternal UPD7 using the methylation-specific \u003ca href=\"https://www.sciencedirect.com/topics/medicine-and-dentistry/multiplex-ligation-dependent-probe-amplification\" title=\"Learn more about multiplex ligation dependent probe amplification from ScienceDirect's AI-generated Topic Pages\"\u003emultiplex ligation dependent probe amplification\u003c/a\u003e (MS-MLPA).\u003c/p\u003e\n\u003cp\u003eMS-MLPA revealed that the relative copy numbers of the three methylation probes in \u003cem\u003eMEST\u003c/em\u003e gene (maternal methylation gene region, paternal methylation was preferentially expressed) were 0.66, 0.66 and 0.64, respectively, suggesting a possible low proportion mosaic UPD (7) mat. However, the experimental results are near the threshold range, so it cannot be interpreted accurately.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3137002/v1/abdbceba02d4bfb179521379.png"},{"id":40911460,"identity":"0e7c8529-386a-4d9d-b004-771916c1f5ea","added_by":"auto","created_at":"2023-08-01 22:46:10","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":88517,"visible":true,"origin":"","legend":"\u003cp\u003eTrio whole exome sequencing results for case 15. The female infant harbored a de novo heterozygous mutation, NM _000095: c.1417_1419dup(p.D473dup), in \u003cem\u003eCOMP \u003c/em\u003ein the female infant.\u003c/p\u003e\n\u003cp\u003eA: The female infant; B: The mother; C: The father\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-3137002/v1/a5134ff4185c85b20e67590d.png"},{"id":40911459,"identity":"8491c415-2d18-4e66-8e9a-dc8cb69a41b2","added_by":"auto","created_at":"2023-08-01 22:46:10","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":99627,"visible":true,"origin":"","legend":"\u003cp\u003eTrio whole exome sequencing results for case 18. The fetus harbored a de novo missense variant, NM_000088: c.1436G\u0026gt;C p.G479A, in \u003cem\u003eCOL1A1 \u003c/em\u003e(120150) on chromosome 17.\u003c/p\u003e\n\u003cp\u003eA: The fetus; B: The mother; C: The father\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-3137002/v1/5e4722398d224201f6dfe9d7.png"},{"id":40911463,"identity":"d075813c-78e0-41a6-9e8a-cbde19e6545b","added_by":"auto","created_at":"2023-08-01 22:46:10","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":142733,"visible":true,"origin":"","legend":"\u003cp\u003eTrio whole-exome sequencing results for case 29. The fetus harbored an inherited paternally splicing variant, NM_000088.4: c.1615-1G\u0026gt;T (p. G802V), in \u003cem\u003eCOL1A1\u003c/em\u003e (120150) on chromosome 17.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-3137002/v1/517379ebfe4d615bc62d6bf4.png"},{"id":50313997,"identity":"6d877ab2-4a0b-4643-8cdc-37932bb3a357","added_by":"auto","created_at":"2024-01-29 15:28:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1587376,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3137002/v1/88cda960-631b-4051-9ac8-ca7a2db0632a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Genetic Testing of Fetal Loss of Heterozygosity Using Single Nucleotide Polymorphism Array and Whole Exome Sequencing","fulltext":[{"header":"Background","content":"\u003cp\u003eIn the prenatal diagnostic setting, chromosomal microarray analysis (CMA) improved the diagnostic rate for chromosomal abnormalities by 4.1\u0026ndash;10% compared with traditional karyotyping in fetuses with ultrasound anomalies (UA). Single nucleotide polymorphism array technology can not only identify copy number variation (CNV) but also detect chromosome aneuploidy and haploidy, triploidy, loss of heterozygosity (LOH), uniparental disomy (UPD), and low-level mosaicism\u003csup\u003e1,2\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eLOH, referred\u0026ensp;to\u0026ensp;as\u0026ensp;the region of homozygosity in a chromosome, and concerns identity by descent (IBD) and UPD. When LOH is confirmed to have been inherited from only one parent, it is called UPD, which can lead to imprinting disorders involving imprinted chromosomes 6, 7, 11, 14, 15, and 20. Moreover, UPDs were classified as either isodisomy, heterodisomy, or mixed UPD, according to the parental origin. Common mechanisms resulting in UPD include trisomy rescue, monosomy rescue, and somatic mitotic recombination, resulting in mosaic segmental UPD\u003csup\u003e3,4\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIt is challenging to assess the prognosis of fetuses with LOH in prenatal diagnosis. Thus, understanding its clinical significance is necessary due to the phenotypic complexity of LOH and its uncertain pathogenicity. To assess the clinical significance and better understand the correlation between LOH and its phenotype, we investigated the clinical manifestations, performed further molecular genetic analysis using parental SNP array verification, trio whole exome sequencing (WES) and Methylation-specific multiplex ligation dependent probe amplification (MS-MLPA), and tracked the perinatal outcomes of fetuses with LOH.\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cp\u003e\u003cstrong\u003eSubjects\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe\u0026nbsp;retrospectively\u0026nbsp;reviewed pregnant women undergoing invasive\u0026nbsp;diagnostic procedure\u0026nbsp;for\u0026nbsp;a variety\u0026nbsp;of\u0026nbsp;indications\u0026nbsp;at all prenatal diagnosis centers in Fujian Province in southeastern China, Fujian Medical University, China, from\u0026nbsp;December\u0026nbsp;2016\u0026nbsp;to\u0026nbsp;December\u0026nbsp;2021.\u0026nbsp;Most of the cases came from Fujian Maternity and Child Health Hospital. Obtaining informed\u0026nbsp;consent from all the pregnant couples, fetal samples were collected via invasive diagnostic procedure\u0026nbsp;according different weeks of gestation.\u0026nbsp;The study was approved by the Ethics Committee of\u0026nbsp;the\u0026nbsp;Fujian Maternity and Child Health Hospital\u0026nbsp;(No.2016KYLLD01051).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConventional karyotyping analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKaryotyping was performed following the standard\u0026nbsp;cytogenetic protocol, and karyotypes were scanned on Leica GSL120. At least 20 metaphases were counted, and five metaphases were analyzed.\u0026nbsp;Karyotype\u0026nbsp;analysis and description\u0026nbsp;were based on ISCN 2020.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIsolation of genomic DNA\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFetal sample, 15 mg of chorionic villi, 30-40\u0026nbsp;mL of\u0026nbsp;amniotic fluid, or 2-5 mL\u0026nbsp;umbilical cord blood\u0026nbsp;was\u0026nbsp;obtained, and\u0026nbsp;genomic DNA from the fetus and its parents were extracted using the QIAamp\u0026reg; DNA Blood Mini Kit (Qiagen Inc., Hilden, Germany) following the manufacturer\u0026rsquo;s instructions, and maternal cell contamination was ruled out using microsatellite DNA linkage analysis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eS\u003c/strong\u003e\u003cstrong\u003eingle\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003enucleotide polymorphism\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;array\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;and data analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eChromosomal aberrations,\u0026nbsp;CNVs and\u0026nbsp;LOH were detected using a\u0026nbsp;SNP\u0026nbsp;array on a CytoScan\u0026nbsp;750K\u0026nbsp;(Affymetrix Inc., Santa Clara, CA)\u0026nbsp;platform containing\u0026nbsp;200 000\u0026nbsp;SNPs and\u0026nbsp;550 000 CNVs\u0026nbsp;probes,\u0026nbsp;all\u0026nbsp;the experimental processes of SNP array were performed as previously described\u003csup\u003e5\u003c/sup\u003e.\u0026nbsp;After obtaining informed consent, parental\u0026nbsp;SNP array verification\u0026nbsp;was\u0026nbsp;performed\u0026nbsp;to\u0026nbsp;confirm\u0026nbsp;the\u0026nbsp;origin\u0026nbsp;of\u0026nbsp;fetal\u0026nbsp;LOH.\u003c/p\u003e\n\u003cp\u003eThe raw data were\u0026nbsp;analyzed using the\u0026nbsp;Affymetrix Chromosome Analysis Suite software (version 3.1.0.15).\u0026nbsp;The\u0026nbsp;coordinate\u0026nbsp;of the chromosome was described based\u0026nbsp;on the genome version hg19. CNVs were\u0026nbsp;classified according to the American College of Medical\u0026nbsp;Genetics (ACMG) guidelines\u003csup\u003e6\u003c/sup\u003e.\u0026nbsp;The reporting threshold was set at CNV \u0026ge; 500 Kb and\u0026nbsp;10 Mb size as the threshold of LOH or over 5 Mb\u0026nbsp;for a terminal\u0026nbsp;fragment\u0026nbsp;LOH occurred in imprinted chromosomes (chromosome 6, 7, 11, 14, 15 and 20).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe significance of\u0026nbsp;LOH results was interpreted\u0026nbsp;through\u0026nbsp;PubMed (http://www.ncbi.nlm.nih.gov/pubmed), Online\u0026nbsp;Mendelian Inheritance in\u0026nbsp;Man (OMIM;\u0026nbsp;http://www.omim.org/), DECIPHER (https://decipher\u0026nbsp;.sanger.ac.uk/), UCSC (http://genome.ucsc.edu/), ClinGen Dosage Sensitivity Map (https://www.ncbi.nlm.nih.gov/projects/dbvar/clingen/index.shtml), uniparental disomy (http://cs-tl.de/DB/CA/UPD/0-Start.html), Geneimprint (http://www.geneimprint.com/), the\u0026nbsp;Catalogue of Imprinted Genes\u0026nbsp;(www.otago.ac.nz/IGC),\u0026nbsp;the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk/ac/index.php), the Locus-Specific Mutation\u0026nbsp;Database (http://www.hgvs.org/dblist/glsdb.htm) and the\u0026nbsp;1000 Genomes Project Dataset (https://www.ncbi.nlm\u0026nbsp;.nih.gov/variation/tools/1000genomes/).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWES and bioinformatics analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo\u0026nbsp;identify\u0026nbsp;homozygous mutations\u0026nbsp;of recessive diseases in addition to UPD,\u0026nbsp;trio-WES (for fetuses and parents) was\u0026nbsp;carried out with\u0026nbsp;the informed consent of pregnant couples.\u0026nbsp;After the\u0026nbsp;sample\u0026nbsp;genomic\u0026nbsp;DNA was\u0026nbsp;extracted,\u0026nbsp;exon capture was conducted using Agilent Sure Select Technology (Agilent, Santa Clara, CA, USA),\u0026nbsp;fragmented randomly, purified, and enriched\u0026nbsp;to construct DNA libraries.\u0026nbsp;Paired-end sequencing was performed on Illumina HiSeq 2500 (Illumina, USA) instruments\u0026nbsp;according to\u0026nbsp;the manufacturer\u0026rsquo;s\u0026nbsp;instructions\u0026nbsp;(Illumina, San Diego, CA, USA).\u003c/p\u003e\n\u003cp\u003eFor sequence alignment, variant calling, and annotation, the sequences were mapped to their location with the human genome reference sequence (hg19 build) using Burrows-Wheeler\u0026nbsp;software (version 0.59)\u003csup\u003e7\u003c/sup\u003e.\u0026nbsp;All SNVs and InDels were annotated with public population frequency databases, including NCBI dbSNP, 1000 Genomes Project, the Exome Aggregation Consortium, as well as OMIM, Swiss-var, Human Gene Mutation Database, ClinVar, and other disease databases, and only variants that were clinically or potentially relevant to the patients\u0026rsquo; phenotype were reported. Annotation of mutations, prediction of protein function effects and shear harmousness were conducted and the pathogenicity of the variants was assessed according to ACMG\u003csup\u003e8\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMS-MLPA\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMethylation analysis of 7q21.13q36.3 loci was performed by MS-MLPA (SALSA MS-MLPA probe mix ME030-C3 BWS/RSS (MRC Holland, Amsterdam, The Nederland\u0026rsquo;s)), and the relative copy numbers of the three methylation probes in the \u003cem\u003eMEST\u0026nbsp;\u003c/em\u003egene (maternal methylation gene region, paternal methylation was preferentially expressed)\u0026nbsp;on chromosome 7q32.2\u0026nbsp;was\u0026nbsp;determined.\u0026nbsp;All procedures were performed following the manufacturers\u0026rsquo; protocols performed as previously described\u003csup\u003e9\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePregnancy outcome\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn\u0026nbsp;fetuses\u0026nbsp;with\u0026nbsp;LOH,\u0026nbsp;we collected data relating to basic information,\u0026nbsp;imaging\u0026nbsp;findings, serological Down\u0026apos;s screening results,\u0026nbsp;non-invasive prenatal testing (NIPT) results, results of\u0026nbsp;invasive diagnostic testing, further genetic analysis,\u0026nbsp;perinatal\u0026nbsp;outcomes, and follow-up\u0026nbsp;information.\u0026nbsp;Perinatal\u0026nbsp;outcomes were obtained from delivery records\u0026nbsp;in our hospital. Otherwise, data relating to\u0026nbsp;other cases\u0026nbsp;from other centers\u0026nbsp;were followed up via\u0026nbsp;telephone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSPSS software version 22.0 (SPSS, Inc., Chicago, IL) was used for statistical analysis.\u0026nbsp;Measurement data were expressed as mean \u0026plusmn; standard deviation,\u0026nbsp;statistical comparisons were performed using\u0026nbsp;\u0026chi;\u003csup\u003e2\u003c/sup\u003e test and\u0026nbsp;Fisher\u0026rsquo;s exact test,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003ePatient characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA\u0026nbsp;total of 11062\u0026nbsp;fetuses undergoing invasive\u0026nbsp;diagnostic testing over a period of 5 years\u0026nbsp;were analyzed using SNP\u0026nbsp;array, and\u0026nbsp;there were 106 fetuses with LOH. The detection rates of fetal LOH for different invasive diagnostic indications\u0026nbsp;are\u0026nbsp;depicted\u0026nbsp;in Table 1.\u0026nbsp;The\u0026nbsp;mean weeks of gestation\u0026nbsp;and maternal\u0026nbsp;age for pregnancies with fetal LOH was\u0026nbsp;21\u0026plusmn;1 (range, 11\u003csup\u003e+6\u003c/sup\u003e to 31) and\u0026nbsp;31\u0026plusmn;3\u0026nbsp;(range,\u0026nbsp;19\u0026ndash;42) years, respectively.\u0026nbsp;The\u0026nbsp;detailed\u0026nbsp;parental SNP array verification\u0026nbsp;results,\u0026nbsp;trio-WES results, MS-MLPA result, ultrasound findings,\u0026nbsp;and\u0026nbsp;perinatal\u0026nbsp;outcomes\u0026nbsp;of 42 fetuses with LOH are summarized\u0026nbsp;in Table\u0026nbsp;2, and the data regarding the remaining 64\u0026nbsp;prenatally diagnosed\u0026nbsp;cases with LOH that declined further genetic testing\u0026nbsp;are listed in Table\u0026nbsp;3.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFetal LOH detected by SNP array\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe overall flow of fetal LOH analysis is illustrated in Fig. 1. The detection rate of fetuses with LOH\u0026nbsp;\u003cem\u003e\u0026ge;\u003c/em\u003e10\u0026nbsp;Mb\u0026nbsp;or\u0026nbsp;\u003cem\u003e\u0026ge;\u003c/em\u003e5\u0026nbsp;Mb\u0026nbsp;involving imprinting regions\u0026nbsp;was 0.96% (106/11 062).\u0026nbsp;In 88 (83.0%)\u0026nbsp;fetuses,\u0026nbsp;LOH occurred\u0026nbsp;on a single chromosome, while in\u0026nbsp;18 (17.0%)\u0026nbsp;fetuses,\u0026nbsp;multiple\u0026nbsp;LOHs\u0026nbsp;were detected on\u0026nbsp;different\u0026nbsp;chromosomes.\u0026nbsp;Of the\u0026nbsp;18\u0026nbsp;cases\u0026nbsp;with multiple\u0026nbsp;LOHs,\u0026nbsp;two cases (Cases 1 and 64) were confirmed\u0026nbsp;from\u0026nbsp;consanguineous couples,\u0026nbsp;and the\u0026nbsp;remaining\u0026nbsp;16\u0026nbsp;cases\u0026nbsp;denied consanguineous miscarriage.\u003c/p\u003e\n\u003cp\u003eWhen\u0026nbsp;LOH occurred\u0026nbsp;on a single chromosome, chromosomes 6\u0026nbsp;(11.4% (10/88)), 3\u0026nbsp;(10.2% (9/88)), and 5\u0026nbsp;(8.0% (7/88))\u0026nbsp;were the most frequently involved, followed by chromosomes\u0026nbsp;15 (6.8%\u0026nbsp;(6/88)),\u0026nbsp;2\u0026nbsp;(6.8%\u0026nbsp;(6/88)), 8\u0026nbsp;(6.8%\u0026nbsp;(6/88)),\u0026nbsp;and 13\u0026nbsp;(6.8%\u0026nbsp;(6/88)) (Tables\u0026nbsp;2 and 3).\u0026nbsp;LOH\u0026nbsp;identified\u0026nbsp;almost the entire chromosome in\u0026nbsp;seven cases, and the\u0026nbsp;involved\u0026nbsp;chromosomes were chromosomes\u0026nbsp;2, 6, 13, 14, 18, and 22. In other cases,\u0026nbsp;LOH\u0026nbsp;occurred in a partial fragment of the chromosome, ranging\u0026nbsp;from\u0026nbsp;5.18\u0026nbsp;Mb to\u0026nbsp;96.8\u0026nbsp;Mb. In total,\u0026nbsp;four\u0026nbsp;cases\u0026nbsp;of\u0026nbsp;mosaic\u0026nbsp;LOH were\u0026nbsp;identified, including in chromosomes\u0026nbsp;13 and 14,\u0026nbsp;5q11.1q35.3, and 7q21.13q36.3, respectively. The mosaicism rate ranged from\u0026nbsp;30% to 80%.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBoth\u0026nbsp;cases\u0026nbsp;(Cases 22 and 28)\u0026nbsp;with\u0026nbsp;LOH on the entire chromosome 6 presented with fetal growth restriction (FGR), and were further diagnosed as paternal UPD6 and maternal UPD6, respectively.\u0026nbsp;Finally, both patients elected termination of pregnancy\u0026nbsp;(TOP) (Table\u0026nbsp;2).\u0026nbsp;Isolated\u0026nbsp;segmental LOH on\u0026nbsp;chromosome\u0026nbsp;6\u0026nbsp;was\u0026nbsp;identified\u0026nbsp;in\u0026nbsp;10 cases, of which\u0026nbsp;nine\u0026nbsp;presented with\u0026nbsp;UAs, including\u0026nbsp;FGR,\u0026nbsp;thickened nuchal translucency (NT), enhanced bowel echo, intracardiac echogenic focus, increased umbilical artery resistance index, oligohydramnios, cervical lymphatic hygroma,\u0026nbsp;mild regurgitation of tricuspid valve,\u0026nbsp;fetal bilateral renal enlargement, increased renal echogenicity,\u0026nbsp;reverse a-wave of ductus venosus, and enhanced intestinal echo,\u0026nbsp;resulting in TOP (\u003cem\u003en\u003c/em\u003e=6)\u0026nbsp;and\u0026nbsp;preterm birth\u0026nbsp;(\u003cem\u003en\u003c/em\u003e=1).\u0026nbsp;The\u0026nbsp;other\u0026nbsp;three cases\u0026nbsp;had a favorable outcome.\u003c/p\u003e\n\u003cp\u003eIsolated\u0026nbsp;LOH on\u0026nbsp;chromosome\u0026nbsp;3\u0026nbsp;was\u0026nbsp;identified\u0026nbsp;in\u0026nbsp;nine\u0026nbsp;cases, of which\u0026nbsp;only two\u0026nbsp;presented with UAs, including\u0026nbsp;thickened NT,\u0026nbsp;resulting in\u0026nbsp;abortion\u0026nbsp;(\u003cem\u003en\u003c/em\u003e=1).\u0026nbsp;The\u0026nbsp;other\u0026nbsp;seven cases\u0026nbsp;showed no anomalies\u0026nbsp;on prenatal ultrasound and had no obvious abnormal phenotypes\u0026nbsp;after birth.\u003c/p\u003e\n\u003cp\u003eIsolated\u0026nbsp;fetal LOH on\u0026nbsp;chromosome\u0026nbsp;5\u0026nbsp;was\u0026nbsp;identified\u0026nbsp;in\u0026nbsp;seven\u0026nbsp;cases, of which\u0026nbsp;three\u0026nbsp;all had abnormal ultrasound findings, including FGR,\u0026nbsp;small fetal head circumference\u0026nbsp;(HC) for gestation age, lethal bone dysplasia\u0026nbsp;(osteogenesis imperfecta type II),\u0026nbsp;\u0026nbsp;micrognathia, small biparietal diameter (BPD), HC, and femur length (FL) for gestation age,\u0026nbsp;bilateral femoral curvature, less than the normal predictive value -2SD,\u0026nbsp;hydrops fetalis, fetal giant bladder,\u0026nbsp;fetal lung cystic adenoma, resulting in TOP (n=3) or\u0026nbsp;preterm birth\u0026nbsp;(n=1), and missed abortion (n=2); the\u0026nbsp;other\u0026nbsp;case\u0026nbsp;(Case 34)\u0026nbsp;showed\u0026nbsp;minor\u0026nbsp;abnormal phenotypes\u0026nbsp;on prenatal ultrasound, and\u0026nbsp;presented\u0026nbsp;micrognathia after birth.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eUAs in fetal\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eLOH detected by SNP array\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTotally,\u0026nbsp;66\u0026nbsp;fetuses presented UAs, including\u0026nbsp;22\u0026nbsp;(33.3%) with structural abnormalities,\u0026nbsp;24\u0026nbsp;(36.4%)\u0026nbsp;with ultrasonic soft marker,\u0026nbsp;18\u0026nbsp;(27.3%) with\u0026nbsp;FGR\u0026nbsp;and\u0026nbsp;9\u0026nbsp;(13.6%) with other presentations. The\u0026nbsp;most common\u0026nbsp;soft marker anomaly was thickened NT.\u0026nbsp;The\u0026nbsp;most frequent ultrasonic structural anomalies\u0026nbsp;were\u0026nbsp;cardiovascular (9.1%),\u0026nbsp;skeletal\u0026nbsp;(6.1%), and\u0026nbsp;genitourinary malformations (6.1%).\u0026nbsp;In the group with UAs,\u0026nbsp;fetal LOH\u0026nbsp;mostly involved chromosomes\u0026nbsp;5, 6, and 1,\u0026nbsp;whereas\u0026nbsp;LOH mostly occurred on chromosomes\u0026nbsp;3, 10, and 18\u0026nbsp;in the group without UAs (Tables 2\u0026nbsp;and 3).\u003c/p\u003e\n\u003cp\u003eFGR\u0026nbsp;was detected prenatally in\u0026nbsp;18\u0026nbsp;fetuses,\u0026nbsp;of which\u0026nbsp;11\u0026nbsp;had\u0026nbsp;FGR\u0026nbsp;as an isolated ultrasound\u0026nbsp;finding. The most frequently\u0026nbsp;involved chromosome was chromosome\u0026nbsp;6 (n=6) in cases with FGR, followed by chromosomes 7 (n=3) and 17 (n=3).\u0026nbsp;The outcomes of these\u0026nbsp;18\u0026nbsp;fetuses included\u0026nbsp;TOP (n=11), preterm birth\u0026nbsp;(n=3),\u0026nbsp;and term birth\u0026nbsp;(n=4). The incidence of fetal\u0026nbsp;TOP\u0026nbsp;was significantly higher in fetuses with\u0026nbsp;FGR\u0026nbsp;than in those without\u0026nbsp;FGR\u0026nbsp;(61.1%\u0026nbsp;(11/18)\u0026nbsp;\u003cem\u003evs\u0026nbsp;\u003c/em\u003e21.6% (19/88),\u003cem\u003e\u0026nbsp;p\u003c/em\u003e\u0026lt; 0.01)\u0026nbsp;(Tables 2 and 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eUPD results\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo verify the parental source of\u0026nbsp;fetal LOH, 21 cases of\u0026nbsp;fetal LOH were confirmed by parental\u0026nbsp;SNP array analysis, of which\u0026nbsp;two (9.5%)\u0026nbsp;had\u0026nbsp;paternal\u0026nbsp;UPD\u0026nbsp;(Cases 4 and 22) and 12 (57.1%) had maternal UPD, namely, case 4 (UPD 14 pat), case 6 (UPD7 mat), case 14 (mosaic UPD7 mat), case 19 (UPD15 mat), case 21 (UPD 16 mat), case 22 (UPD6 pat), case 24 (UPD15 mat), case 25 (UPD11 mat), case 26 (UPD7p22.3p12.2 mat), and case 30 (UPD11 mat); four cases were confirmed to be IBDs (Cases36-42). Among the 14 cases with UPD, cases 19 and 24 were diagnosed with\u0026nbsp;Prader\u0026ndash;Willi syndrome (PWS), cases 6, 14, 25, 26, and 30 were determined Silver-Russell syndrome (SRS), cases 4 and 22 were diagnosed with Kagami-Ogata syndrome (KOS) and transient neonatal diabetes mellitus, respectively.\u0026nbsp;None of confirmed imprinted genes were detected in the cases 20, 23, 27, and 28 except case 21 (UPD16 mat), thus classifying them variant of uncertain significance (VOUS).\u0026nbsp;Among the 14 UPDs, notably, in case 14,\u0026nbsp;amniocentesis was performed\u0026nbsp;due to fetal\u0026nbsp;right aortic arch with aberrant left subclavian artery as ultrasound indicated, LOH with a size of 70.4 Mb was observed in 7q21.13q36.3 by SNP array (Fig. 2A). First, parental SNP array verification indicated that it is not possible to determine whether source of the LOH on chromosome 7 is paternal or maternal (Fig. 2B); Then, MS-MLPA for the methylation analysis of 7q21.13q3615 loci revealed that the relative copy numbers of the three methylation probes (184 bp, 190 bp and 256 bp) in the \u003cem\u003eMEST\u003c/em\u003e gene (maternal methylation gene region, paternal methylation was preferentially expressed) were 0.66, 0.66, and 0.64, respectively, suggesting a possible low proportion mosaic maternal UPD7 associated with Silver-Russell syndrome (Fig. 2C). However, the experimental result was close to the threshold range; thereby, it could not be\u0026nbsp;determined and interpreted accurately.\u0026nbsp;The fetus was term delivered, feeding difficulties existed after birth, 3 months after delivery at present, the child\u0026apos;s height and development were normal, only light weight\u0026nbsp;(Table 2).\u0026nbsp;\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eTwenty-one cases of\u0026nbsp;fetal LOH were further verified by\u0026nbsp;trio-WES, of which\u0026nbsp;one (4.8%)\u0026nbsp;had\u0026nbsp;paternal\u0026nbsp;UPD\u0026nbsp;and four (19.0%) had maternal UPD.\u0026nbsp;Notably, trio-WES was\u0026nbsp;performed in case 12, and maternal UPD15 associated with PWS was confirmed, and the pregnancy was terminated at\u0026nbsp;28\u0026nbsp;weeks (Table 2).\u0026nbsp;None of the definite imprinted genes observed in the other four UPDs, thus classifying a VOUS.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eKaryotyping results\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKaryotyping was performed successfully in\u0026nbsp;all 106\u0026nbsp;fetuses with\u0026nbsp;LOH. In total,\u0026nbsp;97\u0026nbsp;cases yielded normal\u0026nbsp;results, and nine cases had abnormal karyotyping results, including 47,XX,+mar dn, 46,X,i(Xq)[40]/45,X[14], 46,XX,t(4;5)(q31;q23)pat, 46,XY,t(11;22)(q24.1;q12.3) dn, 47,XX,+21, mos 47,XY,+22[3]/46,XY[58], 46,XX,t(12;21)(q12;q22.2) mat, 47,XN,+mar[57]/46,XN[41] and 46,X,inv(Y)(p11.2q11.2) mos 45%.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGene mutation results\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTrio-WES was performed in\u0026nbsp;21\u0026nbsp;cases to detect gene mutation of autosomal recessive diseases\u0026nbsp;in addition to UPD,\u0026nbsp;and\u0026nbsp;11\u0026nbsp;results were\u0026nbsp;clinically\u0026nbsp;significant, including 5 pathogenic variants, 4 likely pathogenic variants and 2 pathogenic UPDs. Among these clinically significant results, three cases (Cases 1, 9, and 15) were identified\u0026nbsp;homozygous mutations in autosomal recessive diseases attributed to LOHs by trio-WES.\u003c/p\u003e\n\u003cp\u003eFor case 11, fetal BPD was small for gestation age by ultrasound, SNP array showed a 38 Mb LOH in 14q13.1q24.2, prenatal trio-WES declined, the fetus was term birthed, the infant was 5 months old now, 60 cm tall, and often arches her back; brain MRI at three months of age revealed that bilateral ventricles were asymmetrical, the left lateral ventricle was larger than the right, some of the extracerebral spaces are slightly widened. Low T1W1 and high T2W1 signals were observed in the bilateral maxillary, ethmoid, and sphenoid sinus.\u0026nbsp;Postnatal trio-WES indicated UPD14 was ruled out, and showed a de novo heterozygous mutation, NM_000095: c.1417_1419dup (p. D473dup), in \u003cem\u003eCOMP\u0026nbsp;\u003c/em\u003ein the female infant (Fig. 3), which is an incidental finding, associated with autosomal dominant pesudoachondroplasia (PSACH, OMIM:177170), epiphyseal dysplasia, multiple, 1(EDM1, OMIM:132400), and carpal tunnel syndrome 2 (CTS2, OMIM:619161).\u0026nbsp;For case 18, amniocentesis was performed, as the fetal left femur was slightly curved, and the SNP array revealed a 20 Mb LOH located in 5q23.2q32. Prenatal trio-WES indicated a de novo missense variant, NM_000088: c.1436G\u0026gt;C p.G479A , in \u003cem\u003eCOL1A1\u003c/em\u003e (120150) on chromosome 17 in the fetus (Fig. 4), associated with osteogenesis imperfecta, type I (OMIM:166200), type II (OMIM:166210), type III(OMIM:259420), type IV (OMIM:166220), Ehlers-Danlos syndrome, arthrochalasia type 1 (OMIM:130060), Caffey disease (OMIM:114000), and bone mineral density variation QTL, steoporosis (OMIM:166710), and the couple elected TOP at 26 weeks.\u0026nbsp;In case 29, amniocentesis was performed, as the fetal bilateral femoral curvature was less than the normal predictive value -2SD was detected on ultrasound, and the SNP array revealed a 46.1 Mb LOH located in 5p15.33p11. Prenatal trio-WES indicated an inherited paternally splicing variant, NM_000088.4: c.1615-1G\u0026gt;T (p. G802V), in \u003cem\u003eCOL1A1\u003c/em\u003e (120150) on chromosome 17 in the fetus (Fig. 5), associated with autosomal dominant osteogenesis imperfecta, and the pregnancy was terminated at 23 weeks (Table 2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePerinatal\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eoutcome and follow-up\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe\u0026nbsp;pregnancy\u0026nbsp;outcomes of the 106\u0026nbsp;fetuses with\u0026nbsp;LOH were as\u0026nbsp;follows:\u0026nbsp;67\u0026nbsp;term births (of which\u0026nbsp;two\u0026nbsp;resulted in\u0026nbsp;neonatal\u0026nbsp;death, and one had an abnormal phenotype after birth),\u0026nbsp;29\u0026nbsp;TOPs,\u0026nbsp;three\u0026nbsp;preterm births,\u0026nbsp;two\u0026nbsp;fetal deaths, and\u0026nbsp;five\u0026nbsp;miscarriages.\u0026nbsp;A full-term infant (Case 14) was diagnosed with feeding difficulties that existed after birth, and 3 months after delivery, the child\u0026apos;s height and development were normal, with only low weight.\u0026nbsp;A\u0026nbsp;preterm\u0026nbsp;infant\u0026nbsp;(Case\u0026nbsp;2)\u0026nbsp;was\u0026nbsp;diagnosed\u0026nbsp;with autism\u0026nbsp;postnatally. One fetus (Case 11) showed fetal BPD that was small for gestation age on prenatal ultrasound screening and was delivered vaginally at term. The infant showed growth\u0026nbsp;delay (60 cm tall at 5 months old), hypotonia,\u0026nbsp;and often arched her back.\u0026nbsp;The rate of adverse\u0026nbsp;pregnancy\u0026nbsp;outcomes in fetuses with\u0026nbsp;LOH\u0026nbsp;with UAs was\u0026nbsp;52.4% (22/42),\u0026nbsp;while it was\u0026nbsp;32.8% (21/64)\u0026nbsp;in those that did not show\u0026nbsp;positive ultrasound findings (\u003cem\u003ep\u003c/em\u003e\u003cem\u003e\u0026lt;\u0026nbsp;\u003c/em\u003e0.05).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn our cohort, we investigate the clinical significance of fetal LOH as well as the correlation between fetal LOH and its clinical features. The rate of LOH meeting the report threshold in our study was 0.96%, slightly lower than the 0.97% reported by Liu et al.\u003csup\u003e10\u003c/sup\u003e, which might be attributed to different sample sizes of the study population and the threshold of LOH reported. The threshold in our cohort was set according to the reported study by Hoppman, et al.\u003csup\u003e11\u003c/sup\u003e. In addition, none of clinically significant LOHs occurring in chromosome X were reported due to lack of the adverse family history associated with X-linked disorders. Thereby fetal LOH occurred on a single chromosome, chromosomes 6 and 5 were the most common involved; whereas, Liu et al.\u003csup\u003e10\u003c/sup\u003e showed that LOH was more likely to occur in chromosomes X, 2 and 16. The discordance may be due to the reporting threshold of the fetal LOH studied.\u003c/p\u003e \u003cp\u003eClinically significant imprinting disorders should be valued, especially for UPD involving imprinted chromosomes 6, 7, 11, 14, 15 and 20\u003csup\u003e12,13\u003c/sup\u003e. The clinical significance of UPD is closely associated with the affected imprinted region and genes in addition to parental origin \u003csup\u003e14,15\u003c/sup\u003e. It is unclear whether there is an imprinting effect in UPD 16\u003csup\u003e16\u0026ndash;18\u003c/sup\u003e, the outcomes of the carriers were variable, from normal growth to delayed growth\u003csup\u003e18\u003c/sup\u003e. Notably, in cases 21 and 27, pregnancies confirmed with maternal UPD16 were terminated owing to UAs and abnormal genetic results.\u003c/p\u003e \u003cp\u003eIn our cohort, 62.3% (66/106) of fetuses with LOH presented UAs, and the most common UA was FGR or FGR combined with other indications (18/66 (27.3%)), and the most frequently ultrasound structure anomalies being cardiovascular system malformations (6/66 (9.1%)), skeletal malformations (4/66 (6.1%)), and genitourinary malformations (4/66 (6.1%)). Seventeen percent (18/106) of fetuses with LOH were FGR, UPDs 2, 7, 14, 15, and 16 were the underlying genetic causes of FGR \u003csup\u003e12,19,20\u003c/sup\u003e. The possible pathogenesis encompasses homozygous pathogenic variants in single gene diseases, imprinting effect, or confined placental mosaicism (CPM) \u003csup\u003e21\u003c/sup\u003e. Thus, UPD is one of the possible genetic factors resulting in FGR. Monitoring fetal growth via ultrasound is essential for the management of fetal LOH. Indicative prenatal ultrasound findings can be observed in patients with Beckwith-Wiedemann syndrome and SRS\u003csup\u003e22,23\u003c/sup\u003e. In our cohort, four cases (Cases 6, 25, 26 and 30) with LOH showed FGR or FGR combined with other indications, of which four UPDs were confirmed. The genetic causes underlying FGR were maternal UPD7 and maternal UPD11 associated with SRS\u003csup\u003e12\u003c/sup\u003e, and TOP was elected owing to unfavorable outcomes. Patients with UPD14 showed multiple UAs, resulting in unfavorable outcomes\u003csup\u003e24,25\u003c/sup\u003e. Paternal UPD14 associated with KOS was confirmed in case 4 with polyhydramnios (amniotic fluid index: 38.7 cm), the pregnancy was terminated finally. Notably, the rate of adverse\u0026ensp;pregnancy\u0026ensp;outcomes in fetuses with LOH and UAs (36.4%) was higher than in those without UAs (15.0%) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), our data demonstrate that it is essential that regular ultrasound screening should be examined to closely monitor the development for fetuses with LOH.\u003c/p\u003e \u003cp\u003eLOH also provides certain signs for investigating homozygous variants in autosomal recessive single gene diseases besides UPD and imprinting effects. In three cases in our cohort, pathogenic homozygous variants in single gene diseases were further identified via trio-WES, resulting in UAs. Thereby, trio-WES should be first performed for its ability of UPD verification as well as identifying homozygous mutations simultaneously (Cases 11, 16, and 17). Furthermore, six cases (Cases 2, 11, 16, 17, 18, and 29) with clinically significant variant were detected, which were incidental findings. Our study also shows that trio-WES could identify incidental pathogenic mutations in addition to homozygous variants attributed to LOH. Thereby, Trio-WES should be recommended first for fetal LOH, especially in fetuses with structural anomalies and/or consanguineous parents.\u003c/p\u003e \u003cp\u003eOur cohort had some limitations. First, although it was a retrospective multicenter study, the sample size was not large enough, studies with larger population will be needed, and the follow-up period was not long enough, which might miss some clinical features. Second, the parental origin of LOH was further identified in only 39.6% of cases and none of the cases were further investigated in placental tissues to confirm CPM.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eWe explore the clinical significance and features of fetal LOH. Various molecular genetic testing techniques, such as parental SNP array verification, trio-WES, MS-MLPA, regular and systematic ultrasonic examination, and placental study when necessary, should be comprehensively performed to precisely assess the prognosis of fetal LOH and guide the affected pregnancy management.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the family members who participated in our study. We also appreciate the obstetricians, radiographers, sonographer and pediatricians who offered assistance to our study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHX, LZ and AY prepared the main manuscript; XC, LX, ML, NL, QG, LC, and HH prepared the experiment. All authors have read and approved the final article.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was sponsored by the Joint Funds for the Innovation of Science and Technology, Fujian Province (no.2020Y9149), 2021 Fujian provincial health technology project (no.2021GGA051), and Natural Science Foundation of Fujian Province (no.2022J01421).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data used to support the findings of this study are available from the corresponding author upon request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors confirm that there are no conflicts of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study complied with the principles set forth in the Declaration of Helsinki. It was approved by the Institutional Review Board of Fujian Maternal and Child Health Hospital. Written informed consent was obtained from each patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAcknowledgements Informed consent was obtained from all patients for being included in the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLevy, B.\u003cem\u003e et al.\u003c/em\u003e Genomic imbalance in products of conception: single-nucleotide polymorphism chromosomal microarray analysis. \u003cem\u003eObstetrics and gynecology\u003c/em\u003e \u003cstrong\u003e124\u003c/strong\u003e, 202-209, doi:10.1097/aog.0000000000000325 (2014).\u003c/li\u003e\n\u003cli\u003eSahoo, T.\u003cem\u003e et al.\u003c/em\u003e Comprehensive genetic analysis of pregnancy loss by chromosomal microarrays: outcomes, benefits, and challenges. \u003cem\u003eGenetics in medicine : official journal of the American College of Medical Genetics\u003c/em\u003e \u003cstrong\u003e19\u003c/strong\u003e, 83-89, doi:10.1038/gim.2016.69 (2017).\u003c/li\u003e\n\u003cli\u003eDel Gaudio, D.\u003cem\u003e et al.\u003c/em\u003e Diagnostic testing for uniparental disomy: a points to consider statement from the American College of Medical Genetics and Genomics (ACMG). \u003cem\u003eGenetics in medicine : official journal of the American College of Medical Genetics\u003c/em\u003e \u003cstrong\u003e22\u003c/strong\u003e, 1133-1141, doi:10.1038/s41436-020-0782-9 (2020).\u003c/li\u003e\n\u003cli\u003eLedbetter, D. H. \u0026amp; Engel, E. Uniparental disomy in humans: development of an imprinting map and its implications for prenatal diagnosis. \u003cem\u003eHuman molecular genetics\u003c/em\u003e \u003cstrong\u003e4 Spec No\u003c/strong\u003e, 1757-1764, doi:10.1093/hmg/4.suppl_1.1757 (1995).\u003c/li\u003e\n\u003cli\u003eXue, H.\u003cem\u003e et al.\u003c/em\u003e Detection of copy number variation associated with ventriculomegaly in fetuses using single nucleotide polymorphism arrays. \u003cem\u003eScientific reports\u003c/em\u003e \u003cstrong\u003e11\u003c/strong\u003e, 5291, doi:10.1038/s41598-021-83147-7 (2021).\u003c/li\u003e\n\u003cli\u003eKearney, H. M., Thorland, E. C., Brown, K. K., Quintero-Rivera, F. \u0026amp; South, S. T. American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. \u003cem\u003eGenetics in medicine : official journal of the American College of Medical Genetics\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, 680-685, doi:10.1097/GIM.0b013e3182217a3a (2011).\u003c/li\u003e\n\u003cli\u003eLi, H. \u0026amp; Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. \u003cem\u003eBioinformatics (Oxford, England)\u003c/em\u003e \u003cstrong\u003e25\u003c/strong\u003e, 1754-1760, doi:10.1093/bioinformatics/btp324 (2009).\u003c/li\u003e\n\u003cli\u003eTavtigian, S. V.\u003cem\u003e et al.\u003c/em\u003e Modeling the ACMG/AMP variant classification guidelines as a Bayesian classification framework. \u003cem\u003eGenetics in medicine : official journal of the American College of Medical Genetics\u003c/em\u003e \u003cstrong\u003e20\u003c/strong\u003e, 1054-1060, doi:10.1038/gim.2017.210 (2018).\u003c/li\u003e\n\u003cli\u003eVasconcelos, S., Ramalho, C., Marques, C. J. \u0026amp; Doria, S. Altered expression of epigenetic regulators and imprinted genes in human placenta and fetal tissues from second trimester spontaneous pregnancy losses. \u003cem\u003eEpigenetics\u003c/em\u003e \u003cstrong\u003e14\u003c/strong\u003e, 1234-1244, doi:10.1080/15592294.2019.1634988 (2019).\u003c/li\u003e\n\u003cli\u003eLiu, J.\u003cem\u003e et al.\u003c/em\u003e Absence of heterozygosity detected by single-nucleotide polymorphism array in prenatal diagnosis. \u003cem\u003eUltrasound in obstetrics \u0026amp; gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology\u003c/em\u003e \u003cstrong\u003e57\u003c/strong\u003e, 314-323, doi:10.1002/uog.21951 (2021).\u003c/li\u003e\n\u003cli\u003eHoppman, N., Rumilla, K., Lauer, E., Kearney, H. \u0026amp; Thorland, E. Patterns of homozygosity in patients with uniparental disomy: detection rate and suggested reporting thresholds for SNP microarrays. \u003cem\u003eGenetics in medicine : official journal of the American College of Medical Genetics\u003c/em\u003e \u003cstrong\u003e20\u003c/strong\u003e, 1522-1527, doi:10.1038/gim.2018.24 (2018).\u003c/li\u003e\n\u003cli\u003eKotzot, D. Prenatal testing for uniparental disomy: indications and clinical relevance. \u003cem\u003eUltrasound in obstetrics \u0026amp; gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology\u003c/em\u003e \u003cstrong\u003e31\u003c/strong\u003e, 100-105, doi:10.1002/uog.5133 (2008).\u003c/li\u003e\n\u003cli\u003eEggermann, T., Soellner, L., Buiting, K. \u0026amp; Kotzot, D. Mosaicism and uniparental disomy in prenatal diagnosis. \u003cem\u003eTrends in molecular medicine\u003c/em\u003e \u003cstrong\u003e21\u003c/strong\u003e, 77-87, doi:10.1016/j.molmed.2014.11.010 (2015).\u003c/li\u003e\n\u003cli\u003eRobinson, W. P. Mechanisms leading to uniparental disomy and their clinical consequences. \u003cem\u003eBioEssays : news and reviews in molecular, cellular and developmental biology\u003c/em\u003e \u003cstrong\u003e22\u003c/strong\u003e, 452-459, doi:10.1002/(sici)1521-1878(200005)22:5\u0026lt;452::Aid-bies7\u0026gt;3.0.Co;2-k (2000).\u003c/li\u003e\n\u003cli\u003eLiang, B.\u003cem\u003e et al.\u003c/em\u003e Prenatal diagnosis of fetuses with region of homozygosity detected by single nucleotide polymorphism array: a retrospective cohort study. \u003cem\u003eJournal of human genetics\u003c/em\u003e \u003cstrong\u003e67\u003c/strong\u003e, 629-638, doi:10.1038/s10038-022-01062-9 (2022).\u003c/li\u003e\n\u003cli\u003eHansen, W. F.\u003cem\u003e et al.\u003c/em\u003e Maternal uniparental disomy of chromosome 2 and confined placental mosaicism for trisomy 2 in a fetus with intrauterine growth restriction, hypospadias, and oligohydramnios. \u003cem\u003ePrenatal diagnosis\u003c/em\u003e \u003cstrong\u003e17\u003c/strong\u003e, 443-450, doi:10.1002/(sici)1097-0223(199705)17:5\u0026lt;443::aid-pd82\u0026gt;3.0.co;2-2 (1997).\u003c/li\u003e\n\u003cli\u003eScheuvens, R.\u003cem\u003e et al.\u003c/em\u003e Maternal uniparental disomy of chromosome 16 [upd(16)mat]: clinical features are rather caused by (hidden) trisomy 16 mosaicism than by upd(16)mat itself. \u003cem\u003eClinical genetics\u003c/em\u003e \u003cstrong\u003e92\u003c/strong\u003e, 45-51, doi:10.1111/cge.12958 (2017).\u003c/li\u003e\n\u003cli\u003eKotzot, D. \u0026amp; Utermann, G. Uniparental disomy (UPD) other than 15: phenotypes and bibliography updated. \u003cem\u003eAmerican journal of medical genetics. Part A\u003c/em\u003e \u003cstrong\u003e136\u003c/strong\u003e, 287-305, doi:10.1002/ajmg.a.30483 (2005).\u003c/li\u003e\n\u003cli\u003eYingjun, X.\u003cem\u003e et al.\u003c/em\u003e Chromosomal uniparental disomy 16 and fetal intrauterine growth restriction. \u003cem\u003eEuropean journal of obstetrics, gynecology, and reproductive biology\u003c/em\u003e \u003cstrong\u003e211\u003c/strong\u003e, 1-7, doi:10.1016/j.ejogrb.2016.12.019 (2017).\u003c/li\u003e\n\u003cli\u003eCarmichael, H., Shen, Y., Nguyen, T. T., Hirschhorn, J. N. \u0026amp; Dauber, A. Whole exome sequencing in a patient with uniparental disomy of chromosome 2 and a complex phenotype. \u003cem\u003eClinical genetics\u003c/em\u003e \u003cstrong\u003e84\u003c/strong\u003e, 213-222, doi:10.1111/cge.12064 (2013).\u003c/li\u003e\n\u003cli\u003eWilkins-Haug, L., Quade, B. \u0026amp; Morton, C. C. Confined placental mosaicism as a risk factor among newborns with fetal growth restriction. \u003cem\u003ePrenatal diagnosis\u003c/em\u003e \u003cstrong\u003e26\u003c/strong\u003e, 428-432, doi:10.1002/pd.1430 (2006).\u003c/li\u003e\n\u003cli\u003eBruce, S.\u003cem\u003e et al.\u003c/em\u003e Submicroscopic genomic alterations in Silver-Russell syndrome and Silver-Russell-like patients. \u003cem\u003eJournal of medical genetics\u003c/em\u003e \u003cstrong\u003e47\u003c/strong\u003e, 816-822, doi:10.1136/jmg.2009.069427 (2010).\u003c/li\u003e\n\u003cli\u003eEggermann, T.\u003cem\u003e et al.\u003c/em\u003e Prenatal molecular testing for Beckwith-Wiedemann and Silver-Russell syndromes: a challenge for molecular analysis and genetic counseling. \u003cem\u003eEuropean journal of human genetics : EJHG\u003c/em\u003e \u003cstrong\u003e24\u003c/strong\u003e, 784-793, doi:10.1038/ejhg.2015.224 (2016).\u003c/li\u003e\n\u003cli\u003eWatanabe, T.\u003cem\u003e et al.\u003c/em\u003e Prenatal findings and epimutations for paternal uniparental disomy for chromosome 14 syndrome. \u003cem\u003eThe journal of obstetrics and gynaecology research\u003c/em\u003e \u003cstrong\u003e41\u003c/strong\u003e, 1133-1136, doi:10.1111/jog.12665 (2015).\u003c/li\u003e\n\u003cli\u003eChen, C. L.\u003cem\u003e et al.\u003c/em\u003e Prenatal diagnosis of paternal uniparental disomy for chromosome 14 using a single-nucleotide-polymorphism-based microarray analysis: A case report. \u003cem\u003eJournal of the Formosan Medical Association = Taiwan yi zhi\u003c/em\u003e \u003cstrong\u003e118\u003c/strong\u003e, 739-742, doi:10.1016/j.jfma.2018.12.010 (2019).\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e The detection rate of fatal LOH by SNP array for different invasive testing indications\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cimg src=\"data:image/png;base64,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\" style=\"width: 601px; height: 324.595px;\" width=\"601\" height=\"324.595\"\u003e\u003c/p\u003e\n\u003cp\u003eData are given as\u0026nbsp;\u003cem\u003en\u0026nbsp;\u003c/em\u003e(%).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEach case was classified based on most\u0026nbsp;important indication. Classification of indications arranged from\u0026nbsp;most to least important was as follows:\u0026nbsp;ultrasound structural anomalies, fetal karyotype abnormality,\u0026nbsp;soft marker,\u0026nbsp;positive NIPT results,\u0026nbsp;high risk\u0026nbsp;for Down\u0026apos;s screening, parental\u0026nbsp;genetic factors, consanguinity, previous adverse pregnancy, AMA\u0026nbsp;and others.\u003c/p\u003e\n\u003cp\u003e*\u0026nbsp;If cases\u0026nbsp;number\u0026nbsp;is less than 20, the percentage is not calculated.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e#\u003c/sup\u003eOther ultrasound\u0026nbsp;anomalies\u0026nbsp;included soft-marker anomalies,\u0026nbsp;FGR or fetal overgrowth, hydramnios, hydramnios and abnormal blood flow on doppler\u0026nbsp;ultrasound.\u003c/p\u003e\n\u003cp\u003eLOH, loss of heterozygosity; NIPT, non-invasive prenatal testing; SNP, single nucleotide polymorphism\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e Forty-two fetuses with LOH accepted further genetic testing\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"773\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCase\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGW\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrenatal ultrasound findings/Invasive testing indication\u003c/strong\u003e\u003cstrong\u003e\u0026sect;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFetal karyotype\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFetal LOH region (hg 19) detected by SNP-array \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSize (Mb)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e/Percentage\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(%)*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eResults of further genetic testing\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(classification of pathogenicity)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOutcome\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eOligohydramnios,\u003c/p\u003e\n \u003cp\u003estrephenopodia,\u003c/p\u003e\n \u003cp\u003econsanguineous\u0026nbsp;\u003c/p\u003e\n \u003cp\u003emarriage\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e1p36.33p36.21(888,658-14,505,595) x2 hmz\u003c/p\u003e\n \u003cp\u003e2q11.1q14.3(95,550,957-127,459,321) x2 hmz\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e13.6 Mb \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e31.9 Mb\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(3.69%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003ePrenatal trio-WES indicated a homozygous mutation, NM_000302: c.2071_2072 ins CC (p.R693Qfs*122), in \u003cem\u003ePLOD1\u003c/em\u003e (153454) in the fetus, associated with Ehlers-Danlos syndrome type 1 (OMIM 225400) which was located in the LOH of 1p36.33p36.21, and both parents were heterozygous for this variation (LP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, neonatal death\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eDecreased fetal FL/BPD and FL/HC ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e12q23.3q24.32(106,008,417-126,307,790) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e20.3 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003ePostnatal trio-WES indicated a heterozygous mutation, NM_001356: c.45+1G\u0026gt;C, in \u003cem\u003eDDX3XP\u003c/em\u003e, which is associated with intellectual developmental disorder, X-linked, syndrome, Snijders Blok type (MRXSSB, OMIM:300958) (P)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003ePreterm birth at 36 weeks, BW 2.75 kg diagnosed with hand deformity, autism\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e19+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eFGR？intracardiac echogenic focus, increased umbilical artery resistance index, oligohydramnios\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e6p25.3p23(203,878-13,411,320) x2 hmz\u003c/p\u003e\n \u003cp\u003e6p21.1p11.1(41,305,454-58,726,706) x2 hmz\u003c/p\u003e\n \u003cp\u003e6q11.1q14.1(61,972,918-75,972,465) x2 hmz\u003c/p\u003e\n \u003cp\u003e6q22.31q25.1(123,041,062-149,830,858) x2 hmz (containing imprinted genes \u003cem\u003ePLAGL1\u0026nbsp;\u003c/em\u003e(603044) and\u003cem\u003e\u0026nbsp;HYMAI\u003c/em\u003e (606546))\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e13.2 Mb\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e17.4 Mb\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13.9 Mb\u003c/p\u003e\n \u003cp\u003e26.7 Mb\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003ePrenatal trio-WES indicated mix UPD (6) mat (P)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e26+3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003ePolyhydramnios (AFI 38.7 cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003earr (14)x2 mos hmz (80%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003eMosaicism\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e80%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003eParental SNP array verification indicated UPD (14) pat, which is associated with Kagami-Ogata syndrome (P)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eMultiple malformations, thickened prenasal skin, \u0026quot;fish mouth\u0026quot; shape mouth\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e1p36.11p21.2(26,044,678-99,969,487) x2 hmz\u003c/p\u003e\n \u003cp\u003e3p25.3p14.2(8,746,546-60,897,120) x2 hmz\u003c/p\u003e\n \u003cp\u003e6p25.1p22.1(5,596,983-28,449,315) x2 hmz\u003c/p\u003e\n \u003cp\u003e6q24.2q25.2(143,241,806-155,371,652) x2 hmz\u003c/p\u003e\n \u003cp\u003e7p14.3p11.1(33,991,108-58,019,983) x2 hmz\u003c/p\u003e\n \u003cp\u003e7q11.21q22.1(62,569,501-98,898,149) x2 hmz\u003c/p\u003e\n \u003cp\u003e11p15.1p11.12(17,372,347-51,550,787) x2 hmz\u003c/p\u003e\n \u003cp\u003e11q11q14.1(54,827,207-84,312,637) x2 hmz \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e73.9 Mb \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e60 Mb\u003c/p\u003e\n \u003cp\u003e22.9 Mb\u003c/p\u003e\n \u003cp\u003e12.1 Mb\u003c/p\u003e\n \u003cp\u003e22.8 Mb\u003c/p\u003e\n \u003cp\u003e24 Mb\u003c/p\u003e\n \u003cp\u003e34.2 Mb\u003c/p\u003e\n \u003cp\u003e29.5 Mb\u003c/p\u003e\n \u003cp\u003e(10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003ePostnatal trio-WES indicated a homozygous mutation, NM_173076.3: c.6577_657 del, in \u003cem\u003eABCA12\u003c/em\u003e in the fetus, associated with autosomal recessive congenital ichthyosis type 4B type (OMIM 242500) and 4A type (OMIM 601277) (P)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eBW 3.2 kg.\u003c/p\u003e\n \u003cp\u003eThe collodion female baby died five days after birth\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e13\u003csup\u003e+6\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eFGR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e7q31.31q36.3(120138084_159118443) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e39 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003eParental SNP array verification indicated UPD (7) mat, which is associated with Silver-Russell syndrome (P)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e18\u003csup\u003e+\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eAMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e2q22.3q31.1(144,624,648-173,171,481) x2 hmz\u003c/p\u003e\n \u003cp\u003e4q13.1q21.3(63,730,113-87,252,596) x2 hmz \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e28.5 Mb\u003c/p\u003e\n \u003cp\u003e23.5 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003ePrenatal trio-WES indicated no clinically relevant mutations.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth\u003c/p\u003e\n \u003cp\u003e(Normal phenotype)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e23\u003csup\u003e+\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eSmall fetal BPD and HC for gestation age\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e14q32.11q32.31(91556694_101593701) x2 hmz\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e10 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003ePrenatal trio-WES indicated no clinically relevant mutations.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth\u003c/p\u003e\n \u003cp\u003e(Normal phenotype)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eFetal ARSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e1p36.21p35.2(15,728,288-31,781,279) x2 hmz\u003c/p\u003e\n \u003cp\u003e4p15.2p11(25,981,952-49,063,479) x2 hmz \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e16 Mb\u003c/p\u003e\n \u003cp\u003e23 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003ePrenatal trio-WES indicated no clinically relevant mutations., and identified a homozygous mutation, NM_015378: c.427A\u0026gt;G (p.R143G), in \u003cem\u003eVPS13D\u003c/em\u003e in the fetus, associated with autosomal recessive spinocerebellar, ataxia, autosomal recessive 4 (SCAR4, OMIM 607317) (VOUS)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth\u003c/p\u003e\n \u003cp\u003e(Normal phenotype)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eFetal bilateral renal enlargement, increased renal echogenicity\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e8q11.23q24.3(55365228_146292734) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e90.9 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003ePrenatal trio-WES indicated UPD (8q11.23-q24.3) mat (VOUS)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth\u003c/p\u003e\n \u003cp\u003e(Normal phenotype)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eSmall fetal BPD was small for gestation age,\u003c/p\u003e\n \u003cp\u003econsanguineous\u0026nbsp;\u003c/p\u003e\n \u003cp\u003emarriage\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e14q13.1q24.2(34435418_72618432) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e38 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003ePostnatal trio-WES confirmed no indication of UPD (14), and showed a heterozygous mutation, NM _000095: c.1417_1419 dup (p.D473dup), in \u003cem\u003eCOMP\u003c/em\u003e in the female infant, associated with autosomal dominant pesudoachondroplasia, (PSACH, OMIM177170), epiphyseal dysplasia, multiple, 1 (EDM1,OMIM 132400), and carpal tunnel syndrome 2 (CTS2, OMIM 619161) (LP)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth\u003c/p\u003e\n \u003cp\u003eNow the infant is 5 months old, 60 cm tall, and often arches her back,\u003c/p\u003e\n \u003cp\u003eBrain MRI revealed that bilateral ventricles were asymmetrical, and the left lateral ventricle was larger than the right. Some of the extracerebral spaces are slightly widened. Low T1W1 and high T2W1 signals were observed in bilateral maxillary sinus, ethmoid sinus and sphenoid sinus.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eFGR; high risk of trisomy 15 detected by NIPT;\u0026nbsp;AMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e15q21.3q26.1(53188649_90583138) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e37.4 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003ePrenatal trio-WES indicated mixed UPD (15q21.3q26.1) mat associated with PWS (P)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eThickened nuchal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003etranslucency (2.8 mm), cervical lymphatic\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ehygroma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e6p12.2p11.1(52607147_58726706) x2 hmz, 6q11.1q12(60972918_66615551) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e6.1 Mb\u003c/p\u003e\n \u003cp\u003e5.6 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003ePrenatal trio-WES indicated no clinically relevant mutations.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eFetal RAA-ARSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e7q21.13q36.3(88,712,610-159,118,443) x2 mos hmz (45%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e70.4 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003eFirst, parental SNP array verification indicated it is not possible to determine whether the LOH of chromosome 7 is paternal or maternal;\u003c/p\u003e\n \u003cp\u003eThen, MS-MLPA for the methylation analysis of 7q21.13q36.1 loci, MS-MLPA revealed that the relative copy numbers of the three methylation probes (184 bp, 190 bp, and 256 bp) in \u003cem\u003eMEST\u003c/em\u003e gene (maternal methylation gene region, paternal methylation was preferentially expressed) were 0.66, 0.66 and 0.64, respectively, suggesting a possible low proportion mosaic UPD (7) mat. However, the experimental results are near the threshold range, so it cannot be interpreted accurately (P) \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth\u003c/p\u003e\n \u003cp\u003eFeeding difficulties exist after birth, now 3 months after delivery, the child\u0026apos;s height and development is normal, only light weight\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e23+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eFetal bilateral renal enlargement, increased renal echogenicity\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e6p12.3q14.1(46587519_77260358) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e27.45 Mb (0.95%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003ePrenatal trio-WES revealed a homozygous mutation, NM_138694.4: c.1233G\u0026gt;A p.K411K, in \u003cem\u003ePKHD1\u003c/em\u003e in the fetus, associated with autosomal recessive polysystic kidney disease 4, with or without hepatic Disease (OMIM 263200) (P)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e21+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eReproductive history of children with chromosomal abnormalities (arr[hg19]9p24.3p22.3(203861_16540793) x1, 9p22.3p13.3(16540940_34942483) x3, which is associated with 9p partial monosomy syndrome and 9p trisomy, respectively; AMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e18p11.32p11.21(136305_15079294) x2 hmz 18q11.1q23(18552517_77997606) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e15 Mb\u003c/p\u003e\n \u003cp\u003e59 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003ePrenatal trio-WES indicated UPD(18) pat, and also revealed a heterozygous splicing mutation, NM_006767.4: c.2069+1G\u0026gt;A, in \u003cem\u003eLZTR1\u003c/em\u003e in the fetus, associated with noonan syndrome 2 (NS10, OMIM 616564）and schwannomatosis-1, susceptibility, (OMIM 615670), inherited paternally (LP)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eCTP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e17\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e18+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eNIPT indicated a 8.2 Mb deletion at 4q31-qter (FF: 6.4 %)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e4q32.3q35.2(167230247_190921709) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e23.7 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003eTrio-WES indicated iso UPD (4q32.3q35.2) mat [(UPD (4)], and also revealed a heterozygous splicing mutation, NM_001807.6, in \u003cem\u003eCEL\u003c/em\u003e in the fetus, associated with maturity-onset diabetes of the young, type VIII (OMIM 609812), inherited paternally (LP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eCurrently developing normally at 2 years old\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e18\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eLethal bone dysplasia\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(osteogenesis imperfecta type II)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e5q23.2q32(125,771,613-145,714,232) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e20 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003ePrenatal trio-WES indicated a de novo missense variant, NM_000088: c.1436G\u0026gt;C p.G479A, in \u003cem\u003eCOL1A1\u0026nbsp;\u003c/em\u003e(120150) on chromosome 17, associated with osteogenesis imperfecta, type I (OMIM166200), type II (OMIM 166210), type III (OMIM 259420), type IV (OMIM 166220), Ehlers-Danlos syndrome, arthrochalasia type 1 (OMIM 130060), Caffey disease (OMIM 114000), and bone mineral density variation QTL, steoporosis (OMIM 166710) (P) \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e28+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eFGR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e15q14q21.3(35,077,111-54,347,324) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e19.2 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003eParental SNP array verification indicated UPD (15) mat, associated with PWS (P)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e27+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eNarrow inner diameter\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;of aortic arch,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eincreased renal echogenicity, FGR, persistent left superior\u0026nbsp;\u003c/p\u003e\n \u003cp\u003evena cava, thickening of the placenta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e2p25.3p11.2(50,813-87,053,152) x2 hmz\u003c/p\u003e\n \u003cp\u003e2q11.1q37.3(95,550,957-242,773,583) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e82.0 Mb\u003c/p\u003e\n \u003cp\u003e147.2 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003eParental SNP array verification indicated UPD (2) mat (VOUS)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e23+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eVSD, FGR, aortic stenosis, left kidney\u0026nbsp;\u003c/p\u003e\n \u003cp\u003edysplasia or absence,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eenhanced intestinal echo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e16q23.2q24.3(79,800,878-90,146,366) x2 hmz\u003c/p\u003e\n \u003cp\u003e16p13.3p12.3(94,807-19,302,326) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e10.3Mb\u003c/p\u003e\n \u003cp\u003e19.2Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003eParental SNP array verification indicated UPD (16) mat (P)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e22+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eFGR, mild tricuspid\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eregurgitation, reverse a-wave of ductus venosus, enhanced intestinal echo\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e6p25.3q27(203,877-170,896,644) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e170.7 Mb\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003eParental SNP array verification indicated UPD (6) pat, associated with transient neonatal diabetes (P)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eAmniocentesis: 47, XX, +mar dn; high risk of trisomy18 screening\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e47, XX, +mar dn\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e3p13p12.1(72,069,483-86,073,653) x2 hmz 3q11.2q22.3(95,320,713-137,634,506) x2 hmz \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e14.0 Mb\u003c/p\u003e\n \u003cp\u003e42.3 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003eParental SNP array verification indicated UPD (3) mat (VOUS)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ecurrently developing normally at 1.5 years old\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eSever FGR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e15q11.2q22.2(22,817,870-62,568,746) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15q26.2q26.3(96,143,558-102,397,317) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e39.7 Mb\u003c/p\u003e\n \u003cp\u003e6.25 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003eParental SNP array verification indicated UPD (15) mat, associated with PWS (P)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eFGR, high risk of trisomy 21 screening\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e11p15.5p15.4(205,827-8,150,933) x2 hmz\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e8 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003eParental SNP array verification indicated UPD (11) mat, associated with Silver-Russell syndrome (P)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eSevere FGR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e7p22.3p12.2(50944_157155880) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e50.4 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003eParental SNP array verification indicated UPD (7p22.3p12.2) mat, associated with Silver-Russell syndrome (P)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eFetal HC was less than the mean 3SD; high risk of trisomy 16 detected by NIPT (Z=18.705)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e16q22.3q24.3(73705779_90146366) x2 hmz \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e16 Mb\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003eParental SNP array verification indicated mixed UPD (16) mat (VOUS)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eFGR; high risk of trisomy 16 detected by NIPT (Z=25.2); AMA,\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e6p25.3q27(203,877-170,896,644) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e170.7 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003eParental SNP array verification indicated mixed UPD (6) mat (VOUS)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eFetal bilateral femoral curvature, less than the normal predictive value -2SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e5p15.33p11(113,576-46,242,541) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e46.1 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003ePrenatal trio-WES indicated an inherited paternally splicing variant, NM_000088.4: c.1615-1G\u0026gt;T (p. G802V), in \u003cem\u003eCOL1A1\u0026nbsp;\u003c/em\u003e(120150) on chromosome 17, associated with autosomal dominant osteogenesis imperfecta (P)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eHydrops fetalis, FGR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, X, i(Xq) [40]/45, X[14]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e11p15.5p15.4(230,750-8,050,928) x2 hmz\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e7 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003eParental SNP array verification indicated UPD (11) mat, associated with Silver-Russell syndrome (P)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eFGR, high risk of trisomy 21 screening\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e7q11.21q11.23(62569502_75233244) x2 hmz 7p14.1p11.1(42421781_58019983) x2 hmz 9q21.13q22.2(78780578_92509057) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e12.7 Mb\u003c/p\u003e\n \u003cp\u003e15.6 Mb\u003c/p\u003e\n \u003cp\u003e13,7 Mb \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003ePrenatal trio-WES indicated no clinically relevant mutations.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ecurrently developing normally at 2 years old\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eHigh risk of trisomy 21 screening\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e7q22.3q31.32(107306055_122301501) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e15 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003ePrenatal trio-WES indicated no clinically relevant mutations.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eCurrently developing normally at 2.5years old..\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eDeep notch a-wave of ductus venosus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e13q14.2q21.2(47358540_61986828) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e14.6 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003ePrenatal trio-WES indicated no clinically relevant mutations.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eCurrently developing normally at 2 years old..\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eFetal micrognathia, small BPD, HC and FL for gestation age\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e5q15q22.1(94849287_110237725) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e15.39 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003ePrenatal trio-WES indicated no clinically relevant mutations.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, micrognathia\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eFetal suprachivalal stenosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e1p31.3p31.1(65532190_78558941) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e13.03 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003ePrenatal trio-WES indicated no clinically relevant mutations.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eFetal pulmonary sequestration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e2p24.3p21(16,435,384-42,306,722) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e25.8 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003eParental SNP array verification indicated IBD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eThickened nuchal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003etranslucency (3.5 mm); AMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e14q11.2q12(22,094,953-32,626,332) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e10.5 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003eParental SNP array verification indicated IBD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003ePregnant women had a child with mental retardation; AMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e3p22.1p14.2(42390369_60178833) x2 hmz \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e17.7 Mb\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003eParental SNP array verification indicated IBD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003ePrevious adverse pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e15q21.2q22.2(49971494_63093257) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e13.1 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003eParental SNP array verification indicated IBD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e18+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eFGR, previous adverse pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e6p21.31p11.1(33808094_58726706) x2 hmz, 6q11.1q16.1(61972918_93717031) x2 hmz\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e24.9 Mb\u003c/p\u003e\n \u003cp\u003e31.7 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003eParental SNP array verification indicated IBD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eAMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e6q14.3q21(87,299,268-110,741,585) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e23.4 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003eParental SNP array verification indicated IBD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.269081500646831%\" valign=\"top\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.677878395860285%\" valign=\"top\"\u003e\n \u003cp\u003eThickened nuchal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003etranslucency (3.0 mm); AMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.408796895213454%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.097024579560156%\" valign=\"top\"\u003e\n \u003cp\u003e1q21.1q21.2(144,077,593-148,750,533) x2 hmz\u003c/p\u003e\n \u003cp\u003e3p21.31p21.1(48,166,782-53,172,233) x2 hmz\u003c/p\u003e\n \u003cp\u003e5q21.3q22.1(107,196,975-110,478,806) x2 hmz 12q21.31q21.33(82,446,525-91,707,400) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14q31.2q32.12(84,339,970-92,755,472) x2 hmz 15q24.1q25.3(73,065,223-87,467,262) x2 hmz 16p13.3(94,807-3,112,982) x2 hmz 17p12p11.2(15,838,698-22,170,994) x2 hmz\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8913324708926265%\" valign=\"top\"\u003e\n \u003cp\u003e54.2 Mb (2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.13195342820181%\" valign=\"top\"\u003e\n \u003cp\u003eParental SNP array verification indicated IBD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.254851228978008%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e*The percentage is calculated by the sum of the size (Mb) of the LOH segments over 5 Mb divided by ~2781 Mb.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026sect;\u003c/strong\u003eEach case was classified based on its most important invasive diagnostic indication. The classification of indications, arranged in the order of importance are as follows: ultrasound anomalies, positive NIPT results, high risk for Down\u0026rsquo; screening, parental abnormal karyotype, consanguinity, previous adverse pregnancies, AMA, suspected fetal infection, and others.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAMA, advanced maternal age; AFI, amniotic fluid index; ARSA, aberrant left subclavian artery; BW, birth weight; BPD, biparietal diameter; FL, femur length; FGR fetal growth restriction; GW, gestational weeks; HC, head circumference; IBD, identity by descent; LOH, loss of heterozygosity; LP, likely pathogenic; Mat, maternal; MS-MLPA, methylation-specific multiplex ligation-dependent probe amplification; NIPT, noninvasive prenatal testing; OMIM, online mendelian inheritance in man; Pat, paternal; P, pathogenic; PWS, prader-willi syndrome; RAA, right aortic arch; SNP, single nucleotide polymorphism; TOP, terminal of pregnancy; UPD, uniparental disomy; VSD, ventricular septal defect\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e The detailed 64 prenatally diagnosed fetuses with LOH declined parental SNP array verification or further genetic testing\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"left\" width=\"746\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCase\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGW\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrenatal imaging findings/Invasive testing indication\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFetal karyotype\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFetal LOH region detected by SNP-array results [hg19]\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSize (Mb)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e/Percentage (%)*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOutcome\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e18+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eHer husband carries 46, XY, t(4;5)(q31;q23), consanguineous marriage\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX, t (4;5) (q31; q23) pat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e18p11.32p11.21(136,304-15,079,294) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e15 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eFGR, enhanced intestinal echo\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e8p23.1p21.3(8117565_21609098) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e13.5 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e23+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eSmall femur length for gestation age; high risk of trisomy 22 detected by NIPT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e22q12.3q13.33(35,156,334-51,157,531) x2 hmz\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e16 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eDel (8p) detected by NIPT; AMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e8p23.3p23.1(168,483-6,999,220) x2 hmz,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8p23.1p12(8,117,564-32,069,805) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e6.8 Mb\u003c/p\u003e\n \u003cp\u003e23.9 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e18+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eConsanguineous marriage;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003epregnant women had a child\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ewith mental retardation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e8p23.3p23.1(2,142,556-6,999,220) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e67.9 Mb (3.63%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth\u003c/p\u003e\n \u003cp\u003eMental retardation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eEnhanced intestinal echo;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePregnant women had three children with cardiac malformation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e13q14.2q22.3(49,157,476-78,073,267) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e29 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eFetal cystic\u0026nbsp;hygroma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e9q21.13q21.33(77,263,747-89,236,178) x2 hmz 9q22.33q31.1(101,366,537-107,749,439) x2 hmz 10q22.3q24.1(80,035,256-97,660,572) x2 hmz 14q31.1q32.2(79,435,542-97,071,550) x2 hmz 17q24.2q25.3(67,002,309-81,041,760) x2 hmz 18q22.3q23(71,555,375-77,997,606) x2 hmz 19q12q13.33(31,360,714-49,513,502) x2 hmz 21q21.1q22.13(19,573,963-39,057,622) x2 hmz \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e111.74 Mb\u003c/p\u003e\n \u003cp\u003e(4.02%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eMissed abortion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e14+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eAMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e9q22.33q33.1(101944435_121284276) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e19.3 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eMissed abortion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eCoarctation of the fetal aorta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e19p13.2p11(6939202_24462369) x2 hmz\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e17.5 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eIntrauterine demise\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eHydrops fetalis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e5q11.1q35.3(49564628_180692321) x2 mos hmz (30%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e130 Mb\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eMissed abortion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eFetal giant bladder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e5q34q35.3(164130490_176629546) x2 hmz\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e12.5 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eMissed abortion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eFetal dysplasia or absence of left radius, abnormal left lower limb posture, single umbilical artery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e16q22.3q24.3(73294159_90146366) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e16.8 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eThickened NT (5 mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e3p14.2p11.1(59365038_90485635) x2 hmz\u003c/p\u003e\n \u003cp\u003e3q11.1q13.11(93558926_103243507) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e31 Mb\u003c/p\u003e\n \u003cp\u003e10 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eMissed abortion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eSmall femur length and humerus\u0026nbsp;\u003c/p\u003e\n \u003cp\u003elength for gestation age\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e4q28.3q31.3(133,718,289-154,569,367) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e20.8 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e26+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eFetal ventriculomegaly (1.4 cm),\u0026nbsp;\u003c/p\u003e\n \u003cp\u003elarge for gestational age\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e3q26.1q29(163,256,369-197,791,601) x2 hmz 5p13.1p11(41,029,137-46,313,469) x2 hmz\u003c/p\u003e\n \u003cp\u003e6q24.2q26(143,341,406-161,527,784) x2 hmz 12q13.2q21.2(56,011,100-77,134,151) x2 hmz\u003c/p\u003e\n \u003cp\u003e17q21.2q21.32(39,639,602-45,479,706) x2 hmz 21q21.3q22.2(28,124,165-42,352,287) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e99.1Mb (3.57%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eFetal infantile polycystic kidney disease?\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e2q31.1q35(175,428,638-216,907,322) x2 hmz, 5q14.3q22.3(85,447,858-113,850,052) x2 hmz \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e41 Mb\u003c/p\u003e\n \u003cp\u003e28 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e28+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eFGR, small fetal HC for gestation age\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e5q15q22.2(94637916_112744413) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e18.1 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003ePreterm birth\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eAMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e10q23.1q25.1(86,546,612-109,956,967) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e23.4 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eFetal tetralogy of Fallot, thickened NT (4.7 mm)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e1p33p32.3(50,051,514-53,274,566) x2 hmz\u003c/p\u003e\n \u003cp\u003e2q23.3q24.1(153,771,280-158,783,675) x2 hmz\u003c/p\u003e\n \u003cp\u003e3q21.2q22.1(124,817,983-129,317,745) x2 hmz\u003c/p\u003e\n \u003cp\u003e3q22.1q23(133,262,566-139,418,898) x2 hmz\u003c/p\u003e\n \u003cp\u003e3q26.1q26.2(161,540,639-168,592,236) x2 hmz\u003c/p\u003e\n \u003cp\u003e7p22.3p21.2(2,707,568-13,857,235) x2 hmz\u003c/p\u003e\n \u003cp\u003e8q23.3q24.12(114,788,423-119,897,611) x2 hmz\u003c/p\u003e\n \u003cp\u003e9p22.1p13.3(19,696,747-36,125,149) x2 hmz\u003c/p\u003e\n \u003cp\u003e11q12.2q12.3(60,193,879-63,210,491) x2 hmz\u003c/p\u003e\n \u003cp\u003e11p11.2p11.12(45,781,075-51,550,787) x2 hmz\u003c/p\u003e\n \u003cp\u003e17q21.31q21.32(41,647,165-44,927,874) x2 hmz\u003c/p\u003e\n \u003cp\u003e17q25.1q25.3(71,965,953-75,785,426) x2 hmz\u003c/p\u003e\n \u003cp\u003e20p11.23p11.21(20,268,153-23,275,237) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e77.5 Mb (2.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e23+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eAmniocentesis: 46,XY,t(11;22)(q24.1;q12.3) dn; AMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY, t (11;22) (q24.1; q12.3) dn\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e3p13q13.31(71,435,373-116,447,779) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e45.0 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eFetal diaphragmatic hernia, permanent right umbilical vein, high risk of trisomy 21 screening\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e22q11.1q13.32(16,888,899-48,538,372) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e31.6 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e19+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eHigh risk of trisomy 21 screening, consanguineous marriage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e8q23.1q23.3(109,495,878-115,007,395) x2 hmz 8q24.21q24.3(128,517,572-143,689,390) x2 hmz 10q24.2q25.1(101,324,364-109,677,582) x2 hmz 11q24.2q25(123,916,776-132,360,867) x2 hmz 16q11.2q12.2(46,504,466-55,451,871) x2 hmz 19q13.12q13.32(36,345,999-45,532,009) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e46.4 Mb (2.89%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eAdverse pregnancy history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e3p26.1p24.1(8,494,626-26,413,121) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e17.9 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e18+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eHigh risk of trisomy 21 screening\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e4q32.1q34.3(161,662,054-181,126,952) x2 hmz\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e19.5 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e19+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eAMA, RSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e15q21.1q24.2(49,174,353-76,415,329) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e27.2 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e30=\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eFetal ventriculomegaly (1.4 cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e1q25.2q31.3(179,562,791-198,041,374) x2 hmz 1p33p32.3(49,189,774-53,588,443) x2 hmz 1p31.1p22.1(83,490,160-94,219,311) x2 hmz 3q22.2q22.3(135,242,870-138,329,862) x2 hmz 3p14.1p13(65,159,530-71,254,193) x2 hmz 3q12.1q12.3(99,386,363-102,630,046) x2 hmz 4q34.3q35.1(178,198,740-183,532,267) x2 hmz 5q33.3q34(157,473,329-162,124,378) x2 hmz 8p21.2p12(25,313,218-29,802,727) x2 hmz 9q22.1q31.2(90,844,062-108,221,369) x2 hmz \u0026nbsp;10q21.1q22.1(54,568,807-72,273,380) x2 hmz 11p11.2p11.12(45,959,522-51,550,787) x2 hmz 13q31.3q32.3(93,816,292-101,526,284) x2 hmz 18q11.1q11.2(18,552,516-23,353,126) x2 hmz 18p11.31p11.21(4,951,983-15,079,294) x2 hmz 20p13p12.3(61,794-5,436,062) x2 hmz \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e129.19 Mb (4.65%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, hydrocephalus, abnormal fingers on both hands, learning disability\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eFetal cleft palate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e8q24.22q24.3(134,714,740-146,292,734) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e11.6 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e18+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eAMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e10q24.32q25.3(104,021,108-115,579,812) x2 hmz\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e11.5 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e19+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eAMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e1p36.12p34.2(22,992,252-40,994,050) x2 hmz\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e18 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e23+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eHydramnios, AMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e2q31.1q32.2(177,156,393-190,026,211) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e12.8 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003ePreterm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e20+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eHigh risk of trisomy 21 screening\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e15q14q21.1(37,475,111-48,299,651) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e10.8 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e22+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eHyperechoic nodules in fetal liver\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e2q11.1q12.3(95,550,957-108,770,463) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e13.2 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eAMA, embryo arrest in one of the twin pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e5q11.1q13.2(49560858_68826246) x2 hmz 5p13.2p11(38119461_46383335) x2 hmz\u003c/p\u003e\n \u003cp\u003e10q11.22q21.1(48654362_59013629) x2 hmz 14q32.2q32.33(98824485_107285437) x2 hmz\u003c/p\u003e\n \u003cp\u003e17q11.1q11.2(25309336_30880382) x2 hmz 17p12p11.1(13895964_22217883) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e19.26 Mb\u003c/p\u003e\n \u003cp\u003e8.26 Mb\u003c/p\u003e\n \u003cp\u003e10.36 Mb\u003c/p\u003e\n \u003cp\u003e8.46 Mb\u003c/p\u003e\n \u003cp\u003e5.57 Mb\u003c/p\u003e\n \u003cp\u003e8.32 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e18+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eAMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e10q22.3q23.33(79424943_95211586) x2 hmz\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e15.79 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eSmall fetal BPD for gestation age, mild tricuspid regurgitation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e6q22.31q23.3(124043730_137024585) x2 hmz\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e12.98 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eAMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e47, XX, +21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003earr (21)x3\u003c/p\u003e\n \u003cp\u003e18p11.32p11.21(136,304-15,079,294) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e14.9 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e21+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eThickened NT (4.7 mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e3p12.3p11.1(78796314_90485635) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e11.7 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e19+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003ePregnant women with mental retardation, night blindness, consanguineous marriage\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e13q13.3q21.33(38088920_71004437) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e32.9 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e25+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eFetal lung cystic adenoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e5q31.3q34(141922621_162299719) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e20 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eFetal enhanced intestinal echo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e1q32.2q44(208165416_245084139) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e36.9 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e18+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eHigh risk of trisomy 1 and trisomy 8 detected by NIPT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e10q23.1q25.1(87343533_109730397) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e22.4 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eFetal slightly thickened pulmonary valve, strephenopodia, pulmonary valve and tricuspid valve mild regurgitation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e3p26.2p25.1(2886527_13828221) x2 hmz 4p16.3p15.33(3473602_14373371) x2 hmz 5p13.3p11(31554333_46313469) x2 hmz \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e10.9 Mb\u003c/p\u003e\n \u003cp\u003e10.9 Mb\u003c/p\u003e\n \u003cp\u003e14.8 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eAbsent fetal nasal bone, high risk of trisomy 18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e2p16.1p13.2(55018895_72337985) x2 hmz 2q11.2q31.1(101324333_177929684) x2 hmz\u003c/p\u003e\n \u003cp\u003e3q13.33q21.3(119592046_128125154) x2 hmz 4q34.3q35.2(181657468_190921709) x2 hmz\u003c/p\u003e\n \u003cp\u003e4q26q31.21(116436130_145124024) x2 hmz 5q23.3q33.3(128032159_157973399) x2 hmz\u003c/p\u003e\n \u003cp\u003e11q11q13.3(54827208_69837254) x2 hmz 11p14.3p11.12(21783630_51550787) x2 hmz\u003c/p\u003e\n \u003cp\u003e12q12q24.31(46091467_124915560) x2 hmz 15q22.31q24.1(66572692_73290903) x2 hmz\u003c/p\u003e\n \u003cp\u003e17p13.3p13.1(1365961_8388179) x2 hmz 17q22q24.1(55220296_64161582) x2 hmz\u003c/p\u003e\n \u003cp\u003e17q24.3q25.3(69423334_81041760) x2 hmz 21q22.12q22.3(36678533_48061211) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e339.6 Mb (12.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003ehypoplastic nasal bone, high risk of trisomy 21 detected by NIPT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e3q12.1q13.2(99160747_111326722) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e12.2 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e18+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eThe husband of the pregnant woman carries 46,XY, t(2;6)(p21;q21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e11p15.5p15.4(230751_5408252) x2 hmz\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e5.18 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eFGR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e3q11.2q13.13(97766775_109823273) x2 hmz 4q27q32.1(121203882_156320512) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e12 Mb\u003c/p\u003e\n \u003cp\u003e35 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003ePreterm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e19+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eDeletion in 1p36.3 detected by NIPT, AMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e1p36.33p36.13(888659_18328851) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e17.4 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eThickened NT (3.2 mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e2q24.3q31.1(164542492_174491805) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e10 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e25+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eFetal portal-body venous shunt outside the liver\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e4p15.2p11(22224153_49063479) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e26.8 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e19+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eHigh risk of trisomy 21 screening\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e8q13.3q21.13(72567811_83036411) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e10.5 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e18+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eDeep notch a-wave of ductus venosus, adverse pregnancy history\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e13q14.2q21.2(47320304_61602456) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e14.3 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eAdverse pregnancy history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e2q11.1q11.2(95550958_100799003) x2 hmz 9p24.1p13.2(8235898_36732597) x2 hmz\u003c/p\u003e\n \u003cp\u003e18q11.2q22.1(23795473_66441448) x2 hmz 20q13.12q13.32(43817586_56736674) x2 hmz\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e89.3 Mb (3.21%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e18+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eHigh risk of trisomy 21 screening\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e18q12.2q21.1(35074699_45621145) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e10.55 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eFetal right ventricle is slightly smaller than the left ventricle, slightly smaller the inner diameter of the pulmonary artery and left and right pulmonary artery, and mild tricuspid regurgitation, high risk of trisomy 21 screening\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003emos 47, XY, +22[3]/46, XY [58]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003earr (22)x2.3 (30% mos)\u003c/p\u003e\n \u003cp\u003e22q12.3q13.33(36679058_51157531) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e14.5 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e19+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eHigh risk of fetal sex chromosome aneuploidy detected by NIPT, AMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e3q13.13q22.2(110489883_134438659) x2 hmz\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e23.9 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eFetal bilateral choroid plexus cysts, intracardiac echogenic focus, high risk of fetal sex chromosome aneuploidy detected by NIPT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e3p13p11.1(72195690_90485635) x2 hmz 3q11.1q12.2(93558926_100589330) x2 hmz\u003c/p\u003e\n \u003cp\u003e4q31.21q32.3(145585354_165933062) x2 hmz 6q26q27(161702754_170896644) x2 hmz\u003c/p\u003e\n \u003cp\u003e11p13p11.12(36146925_51550787) x2 hmz 11q11q12.2(54827208_60193880) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e75.6 Mb\u003c/p\u003e\n \u003cp\u003e(2.72%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e19+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eThe pregnant woman carries 46, XX, t(12;21)(q12;q22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX, t (12;21) (q12; q22.2) mat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e3p12.3q12.2(78304909_100613493) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e22 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e20+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eFetal separation of right renal pelvis, intracardiac echogenic focus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e14q23.2q24.3(62101707_77219310) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e15 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eFetal multiple calcification foci in fetal abdominal cavity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e2q24.1q24.3(156,461,811-165,665,567) x2 hmz 2p13.2p11.2(72,170,192-83,714,557) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e9.2 Mb\u003c/p\u003e\n \u003cp\u003e20.7 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eFetal agenesis of the corpus callosum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e13q21.2q31.1(61,365,983-85,033,012) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e23 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e103\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eFGR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e6q12q14.1(69812646_82725168) x2 hmz \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e12.9 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003ePreterm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e30+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eFGR, amniocentesis: 47,XN,+mar[57]/46,XN[41]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e47, XN, +mar [57]/46, XN [41] dn\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e6p12.3q13(47138118_74152240) x2.77\u003c/p\u003e\n \u003cp\u003e6p25.3p12.3(203877_47207081) x2 hmz\u003c/p\u003e\n \u003cp\u003e6q13q27(74056154_170896644) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e27.0 Mb\u003c/p\u003e\n \u003cp\u003e96.8 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTOP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e29+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eFGR, increased intestinal echo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, XY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003e12p13.2p12.1(10143600_22685434) x2 hmz\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e12.5 Mb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth, normal development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.417670682730924%\" valign=\"top\"\u003e\n \u003cp\u003e106\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.685408299866131%\" valign=\"top\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.954484605087014%\" valign=\"top\"\u003e\n \u003cp\u003eAMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.733601070950467%\" valign=\"top\"\u003e\n \u003cp\u003e46, X, inv(Y) (p11.2q11.2) mos 45%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.718875502008032%\" valign=\"top\"\u003e\n \u003cp\u003earr (13)x2 mos hmz (45%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.843373493975903%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.646586345381525%\" valign=\"top\"\u003e\n \u003cp\u003eTerm birth,\u003c/p\u003e\n \u003cp\u003eepilepsy, mild mental retardation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e*The percentage is calculated by the sum of the size (Mb) of the LOH segments over 5 Mb divided by ~2781 Mb.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026sect;\u003c/strong\u003eEach case was classified based on its most important invasive diagnostic indication. The classification of indications, arranged in the order of importance are as follows: ultrasound anomalies, positive NIPT results, high risk for Down\u0026rsquo; screening, parental abnormal karyotype, consanguinity, previous adverse pregnancies, AMA, suspected fetal infection, and others.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAMA, advanced maternal age; BPD, biparietal diameter; dn, de novo; FGR, fetal growth restriction; hmz, homozygosity; NIPT, noninvasive prenatal testing; NT, nuchal translucency; RSA, recurrent spontaneous abortion; SNP, single nucleotide polymorphism; TOP, termination of pregnancy.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"loss of heterozygosity, prenatal diagnosis, single nucleotide polymorphism array, uniparental disomy, whole exome sequencing","lastPublishedDoi":"10.21203/rs.3.rs-3137002/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3137002/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo explore the clinical significance of fetal loss of heterozygosity (LOH), identified by single-nucleotide polymorphism array (SNP array).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe retrospectively reviewed data form pregnant women who underwent invasivediagnostic procedure at prenatal diagnosis centers in Southeastern China from December 2016 to December 2021. SNP array was performed by the Affymetrix CytoScan 750K array platform. Fetuses with LOH (10 Mb as the threshold or over 5 Mb involving imprinted chromosomes) were further identified by parental verification, MS-MLPA, and/or trio whole exome sequencing (trio-WES), and the genetic results, fetal clinical manifestations, and perinatal outcome were comprehensively analyzed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOf 11 062 fetuses, 106 (0.96%) with LOH exhibiting a neutral copy number were detected; in 88 (83.0%) of these, LOH occurred in a single chromosome, while 18 (17.0%) fetuses had multiple LOHs on different chromosomes. A total of 66 fetuses had ultrasound anomalies (UAs); the most frequent UA was fetal growth restriction (18/66 (27.3%)). Further genetic analysis was performed in 42 cases (21 cases by parental SNP array verification and 21 cases by trio-WES), in which, we found clinically relevant uniparental disomy in 12 cases, pathogenic variants in five cases, likely pathogenic variants in four cases, variant of unknown significance in six cases, and identity by descent in eight cases. Significantly, the rate of adverse pregnancy outcomes in fetuses with LOH and UAs (24/66 (36.4%)) was higher than in those without UAs (6/40 (15.0%)) (\u003cem\u003ep\u003c/em\u003e\u0026lt; 0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFetuses with LOH is not uncommon. Various molecular genetic testing techniques, such as parental SNP array verification, trio-WES, MS-MLPA, regular and systematic ultrasonic monitoring, and the placental study when necessary, should be performed to accurately assess the prognosis of fetal LOH and guide the affected pregnancy management.\u003c/p\u003e","manuscriptTitle":"Genetic Testing of Fetal Loss of Heterozygosity Using Single Nucleotide Polymorphism Array and Whole Exome Sequencing","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-08-01 22:46:05","doi":"10.21203/rs.3.rs-3137002/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2023-10-25T05:22:22+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-09-29T01:30:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"940aa259-1af1-48d3-b738-60400690c732","date":"2023-09-12T13:08:12+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-09-09T07:40:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"2ab7b62b-5849-4647-b732-d266dd56767f","date":"2023-09-01T16:47:52+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-08-02T12:57:05+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-08-01T13:44:16+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2023-07-27T15:32:48+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-07-27T15:29:21+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2023-07-03T22:20:36+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"110e5b3a-6b85-484d-8f5b-650dfbec8cb9","owner":[],"postedDate":"August 1st, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":23611909,"name":"Biological sciences/Genetics"},{"id":23611910,"name":"Health sciences/Medical research"},{"id":23611911,"name":"Health sciences/Molecular medicine"}],"tags":[],"updatedAt":"2024-01-29T15:24:58+00:00","versionOfRecord":{"articleIdentity":"rs-3137002","link":"https://doi.org/10.1038/s41598-024-52812-y","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2024-01-25 15:13:10","publishedOnDateReadable":"January 25th, 2024"},"versionCreatedAt":"2023-08-01 22:46:05","video":"","vorDoi":"10.1038/s41598-024-52812-y","vorDoiUrl":"https://doi.org/10.1038/s41598-024-52812-y","workflowStages":[]},"version":"v1","identity":"rs-3137002","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3137002","identity":"rs-3137002","version":["v1"]},"buildId":"oE6Zbj460LM0Up2FdVbMZ","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}