Prenatal diagnosis and counseling of fetal chromosomes with structural abnormalities

Prenatal diagnosis and counseling of fetal chromosomes with structural abnormalities | 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 Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Prenatal diagnosis and counseling of fetal chromosomes with structural abnormalities Guojian Lv, Yi Liu, Xuecheng Sun, Kai Mu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4372185/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objectives To explore the pregnancy, fertility risk and genetic suggestions of pregnant women with complex structural abnormalities of fetal chromosomes. Study Design Amniotic fluid puncture, chromosome culture of amniotic fluid and chromosome G banding analysis were performed on 9867 pregnant women who came to our hospital for prenatal diagnosis from 2012 to 2023, CMA was performed in 8 pregnant women with complex structural abnormalities in amniotic fluid. Results Chromosome G banding analysis showed that the karyotypes of all 8 cases were structural abnormalities, with deletion and duplication, combined with CMA results, comprehensive analysis showed that case 1 was derived chromosome 3 with deletionof 3p13p14. In case 2, 7q11.23q21.3 was inserted at 4q31.3. Case 3 was derived chromosom 16 with deletion of 16p13.3 and duplication of 18q12.3q23. Case 4 was derived chromosome 9 with duplication of 20p12.1p13. Case 5 was derived chromosome 21 with duplication of 2p22.2p25.3 and 21q11.2q21.3. Case 6 was derived chromosome21 with duplication of 18q12.3q23; Case 7 was derived chromosome 4 with duplication of 4q26q35.2(116376542_188138856) and deletion of 4q35.2(188155531_190957460), and case 8 was derived chromosome X with duplication of Xp22.31p11.1(9041083_58455353) and deletion of Xp22.33p22.31(168552_9040480). Conclusion The combination of G-banding analysis technology and CMA can not only detect the complex structural abnormalities of the amniotic fluid chromosomes, but also determine whether the missing or repeated regions contain important genetic genes. Then, by referring to the results of the parents' chromosomes or the results of ultrasound examination, the abnormalities of fetal chromosomes are summarized and analyzed, so as to obtain clinical consultation opinions. Fetal chromosome structure abnormalities G banding analysis CMA FISH Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Introduction Chromosome structure abnormality is one of the causes of fetal genetic diseases, with the development of society, the probability of fetal chromosome structure abnormality is gradually increasing, the combined application of ultrasound, chromosomal micoarray analysis (CMA), chromosome G banding analysis and fluorescence in situ hybridization(FISH) can significantly improve the probability of finding fetal chromosome structure abnormality, and play a role in the purpose of eugenics and fertility, and improve population quality. Objects and methods 1.1 Research object From January 2012 to December 2023, 9867 pregnant women who came to our hospital for amniocentesis, pregnant women aged 17 to 55 years old, gestational weeks 15 to 35 weeks, due to advanced age, abnormal B-ultrasound, screening or non-invasive high risk of puncture, had been informed of the risk and signed informed consent before puncture. 1.2 Research method G banding analysis technology The sheep water obtained from the puncture was planted in two culture bottles and cultured in an incubator of 5% CO2 at 37℃ for 6–8 days, the medium was changed from 8–10 days, and colchicine was added for 10–12 days to harvest, and the film was finally read after preparation, G-banding and Giemsa staining. According to the ISCN2020 edition, five karyotypes are analyzed, 20 numbers are counted, and if a chimera is encountered, 100 are added. Chromosome microarray analysis The chip design analysis first selects the Affymetrix-based Cyto Scan 750K Array chip, according to the requirements in the operation manual provided by the American Affymetrix public test system, first carried out the amplification of the whole gene sequence, the detection and Analysis of markers and the scanning of the whole genome structure, and then carried out the copy number analysis of the whole genome with the Chromosome Analysis Suite software. Fluorescence in situ hybridization analysis The three probes used in the FISH analysis were: 4p16.3(2,156,895-2,351,734), 7q21.12(86,802,721 − 86,97,97,95, 903) and 7p22.3(1,645,493-1,814,816). The metaphase division phase of each chromosome was analyzed by fluorescence microscope. Ultrasound detection during fetal pregnancy Until the pregnant woman's gestational age reached the appropriate time, ultrasound was used to detect the fetal double parietal diameter, fetal head circumference, heart, brain, kidney, and limbs development. Results 2.1 Fetal chromosome examination Among the 9867 amniotic fluid chromosomes, 8 cases had complex structural abnormalities. Chromosome structural abnormalities in cases 1 , 6 , 7 and 8 came from new mutations (see Table 1 , FIG. 1 a, FIG. 6a, FIG. 7a and FIG. 8a), chromosome structural abnormalities in case 2 came from their mothers (see Table 1 and FIG. 2 a), chromosome structural abnormalities in cases 3 , 4 and 5 were due to the fact that their parents were balanced translocation carriers. It was followed by an unbalanced translocation (see Table 1 , FIG 3a, 4a, 5a). 2.2 Check on the fetal chip The CMA result of case 1 was that arr 3p14.2p12.3(62,450,296 − 79,586,304)x1, 3p14.2p12.3 had 16.34Mb deletion, which contained CADPS, SYNPR, SYNPR-AS1, FHIT, FOXP1 and other genes, there may be developmental delays, mental retardation, multiple deformities and other clinical symptoms (see Fig. 1 b). The CMA result of case 2 was arr[hg19] 7q11.23q21.3(77,283,926 − 93,528,760)x3, 7q11.23q21.3 with 15.5Mb amplification, including SEMA3A, FZD1, CACNA2D1, SLC25A40, SEMA3A, FZD1, CACNA2D1, and SLC25A40, there are 41 OMIM genes, including CYP51A1, SAMD9, which are related to brain neuron development, blood vessel and immune protein expression (see Fig. 2 b). The CMA results of case 3 were arr[hg19] 16p13.3(85,880-1,256,722)x1,18q12.3q23(43,312,367 − 78,013,728)x3, 16p13.3 with 1.17Mb fragment deletion, it contains 36 OMIM genes such as POLR3K, RHBDF1 and MPG, which can present clinical symptoms such as language and mental retardation, atrioventricular septal defect, facial morphological abnormalities, kidney enlargement, and wide thumb, there is 34.7Mb fragment amplification in 18q12.3q23, it contains 105 OMIM genes such as SLC14A1, EPG5, PSTPIP2, and so on, which may have mental retardation and low muscular tone symptoms (see Fig. 3b). CMA results of case 4 were as follows: arr[hg19] 20p13p12.1(61,661 − 13,722,351)x3, 20p13p12.1 had 13.66Mb fragment amplification, which contained 82 OMIM genes including SOX12, NRSN2, TRIB3 and RBCK1, patients may have developmental delays, mental retardation, language disorders, and broad nose (see Fig. 4b). The CMA results of case 5 were arr[hg19] 2p25.3p22.2(12,770 − 37,352,776)x3,21q11.2q21.3(15,016,486 − 31,024,019)x3, 2p25.3p22.2 had 37.34Mb of fragment repeats, it contains 82 OMIM genes such as SOX12, NRSN2, TRIB3, RBCK1, and so on, patients may show developmental delay, mental retardability, language disorder, broad nose bridge and other phenotypes, 21q11.2q21.3 has 16Mb fragment duplication, covering the Early-onset_Alzheimer_disease_with_cerebral_amyloid_angiopathy region and containing 31 OMIM genes such as LIPI, APP, ABCC13 and HSPA13, symptoms of abnormal finger morphology, mental retardation, and developmental delay may occur (see Fig. 5b). The CMA result of case 6 was arr[hg19] 18q12.3q23(37,974,391 − 78,013,728)x3, and there were 40.039Mb replicates in the 18q12.3q23 region, which contained 115 OMIM genes such as PIK3C3, RIT2, SYT4 and SETBP1, symptoms such as stunting, mental retardation, short stature and enlarged heart may occur (Fig. 6b). The CMA results of case 7 were arr[GRCh37]4q26q35.2(116376542_188138856)x3, arr[GRCh37] 4q35.2(188155531_190957460)x1, 4q26q35.2 with 71.762Mb replicates, it contains 179 OMIM genes, including TRAM1L1, NDST3, PRSS12, and so on, which may cause intellectual disability, comprehensive developmental delay, autism, and so on, there is 2.802Mb deletion in the 4q35.2 region, including 3 OMIM genes ZFP42, FRG1, FRG2, this segment had no pathogenic significance (Fig. 7b). The CMA results of case 8 were arr[GRCh37] Xp22.31p11.1(9041083_58455353)x3, arr[GRCh37] Xp22.33p22.31(168552_9040480)x1, there were 49.414Mb repeats in Xp22.31p11.1 region, including 268 OMIM genes such as TBL1X, GPR143, SHROOM2, CLCN4,and so on, and 8.872Mb deletion in Xp22.33p22.31 region, it contains 43 OMIM genes, including PLCXD1, GTPBP6, PPP2R3B, and SHOX, which can cause symptoms such as global stunting, ichthyosis, and short stature (see Fig. 8b). 2.3 Verification of Fish probe Figure 2 c shows that the red fluorescence represents 7p22.3(1,645,493-1,814,816), orange fluorescence represents 7q21.12(86,802,721 − 86,97,97,95,95,903), the green fluorescence represents 4p16.3(2,156,895-2,351,734), ins(4; 7)→ The chromosome indicated indicates that the repeated 7q11.23q21.3 fragment is inserted into the 4q31.1 position, resulting in a derived chromosome 4. 2.4 Fetal ultrasound detection during pregnancy In case 1 , ultrasound examination showed multiple deformities of the fetus, which were consistent with tetralogy of Fallot, hydrocephalus, and double renal dysplasia (see Fig. 1 c, 1 d). In case 2, the fetal ventricular septal defect was detected by ultrasound (see Fig. 2 d). In other cases, no abnormality was detected by ultrasound before abortion. Table 1 Amniotic fluid karyotype and chip detection case Clinical indication Fetal karyotype Parental karyotype CMA ending 1 Husband karyotype 46,XY,inv(1)(p13q21) 46,Xn,inv(1)(p13q21),del(3)(p13p14) Paternal karyotype: 46,XY,inv(1)(p13q21); The mother's karyotype was normal del(3)(p12.3p14.2) is missing 16.34Mb Induction of Labour 2 NIPT shows a 15.54Mb duplication in 7q21.11-q21.3 46,Xn,der(4)ins(4;?)(q31.3;?) Father karyotype normal, mother: 46,XX,der(4)ins(4; ?). (q31.3; ?). dup(7)(q11.23q21.3) repeat 15.5Mb eutocia 3 NIPT shows high risk on chromosome 18 46,Xn,der(16)t(16;18)(p13.3;q12.3) Father karyotype normal, mother: 46,XX,t(16; 18) (p13.3; Q12.3) del(16)(p13.3)missing1.17Mb;dup(18)(q12.3q23) repeat 34.7Mb Induction of Labour 4 Pregnant women have 46,XX,t(9; 22. 20)(q12; p11; p12) 46,Xn,der(9)t(9;22;20)(q12;p11;p12),der(22)t((9;22;20)mat Father karyotype normal, mother: 46,XX,t(9; 22. 20)(q12; p11; p12) dup(20)(p12.1p13) repeat 13.66Mb Induction of Labour 5 NIPT shows high risk of chromosome 21 47,Xn,der(21 )t(2;21)(p22.2;q21.3),+21 Father karyotype normal, mother: 46,XX,t(2; 21) (p22.2; Q21.3) dup(2)(p22.2p25.3) repeat 37.34Mb; dup(21)(q11.2q21.3) repeat 16Mb Induction of Labour 6 Down's screening for chromosome 21 is high-risk 46,Xn,der(21)(18qter→18q12.3::21p13→21qter) The father's karyotype was normal; The mother's karyotype was normal dup(18)(q12.3q23) repeat 40.039Mb Induction of Labour 7 Color ultrasound hint: NT thickening old age 46,Xn,der(4)del(4)(q35.2)dup(4)(q35.2q26)dn The father's karyotype was normal; The mother's karyotype was normal dup(4)(q26q35.2) repeat 71.762Mb; del(4)(q35.2) is missing 2.802Mb Induction of Labour 8 NIPT showed fewer sex chromosomes 46,X,der(X)del(X)(p22.31)dup(X)(p22.31p11.1)dn The father's karyotype was normal; The mother's karyotype was normal dup(X)(p11.1p22.31) repeat 49.414Mb; del(X)(p22.31p22.33) is missing 8.872Mb Induction of Labour Comment It is known that fetal chromosome structural abnormalities generally have three sources, one is a new mutation, one is directly from the parents, and one is because the parents are carriers of balanced translocation, the fetus is unbalanced translocation. Fetal chromosomal structural abnormalities in cases 1 , 6 , 7 , and 8 were new mutations, and labor had been induced. In case 2, the fetal chromosomal structural abnormality originated from the mother and was currently delivered vaginally. The structural abnormalities of fetal chromosomes in cases 3 , 4 , and 5 were due to the fact that their parents were carriers of balanced translocation, resulting in three cases of unbalanced fetal chromosome translocation, which have been aborted. Case 1 in this study was deletion of copy number in the short arm of chromosome 3, similar to this study, Abarca-Barriga HH[ 1 ] found that a Peruvian newborn identified as 3p13p14.1 lost 5.5Mb copy number variation, its clinical symptoms include prolonged eye distance, iridia, microphthalmia, high palate, neurosensory deafness, heart malformation, developmental delay, seizures and nostril atresia, and so on, and the above symptoms are believed to be caused by the deletion of 54 genes such as FOXP1, UBA3, FAM19A1 and MITF, and the missing genes in case 1 completely cover these 54 genes, the symptoms of multiple deformities and developmental delays predicted by CMA were basically consistent with the above Peruvian newborns. Case 6 in this study was a duplication of the long arm part of chromosome 18, similar to this study, Prontera P[ 2 ] found that in a family, a mother and a husband and wife both carried rec dup (18q), showing deformities and short stature, but only the son had symptoms of mild mental retardation and language retardation, this is similar to the CMA prediction of case 6 , which may show symptoms such as developmental delay, intellectual impairment, and short stature. In this study, case 7 had both deletion and duplication of the long arm of chromosome 4. Popescu R[ 3 ] found that a boy had duplication of chromosome 4 in the same region as case 7 , and its clinical characteristics were as follows: flattened occipital region, Slight turbidity, A high, broad forehead, Long eye distance, Deep eyes, Downward-sloping and short palpebral fissure, Epicanthus, Nose protruding, base wide, bulbous tip, Small mouth, Small posterior jaw, large short middle jaw, with prominent relief, Low, protruding ears, the CMA prediction of congenital heart disease was very different from that of case 7 . The Xp22.31p11.1(9041083_58455353) repeat region of case 8 completely covers multiple dose-response regions and dose-response genes, such as the NR0B1 gene included in the Xp21.2 region, which is considered to be a candidate gene involved in XY gonadal hypoplasia if overexpressed[ 4 ], for example, in the study of repetition area p11.23-p11.22, Verbeek S[ 5 ] found that a 13-year-old girl suffered from Xp11.22-p11.23 repetition syndrome, and she presented with severe non-paranoplastic Lambert-Eaton myasthenia syndrome (LEMS). Another missing fragment Xp22.33p22.31(168552_9040480) in case 8 was found by Yin T[ 6 ] in a related study, the CMA test results of a 19-month-old boy indicated that about 8.3Mb fragments of Xp22.33p22.31 were missing, Yq11.221-qter had about 43.3Mb fragment repeats, and its clinical symptoms were short stature, nasal root invagement, bilateral cryptorchidism, and mental retardency. The boy's symptoms were mainly related to the absence of Xp, which was partially consistent with the CMA results of case 8 . In case 2, the region of the long arm of chromosome 7 is repeated at the long arm position of chromosome 4. The cause of trisomy of the long arm part of chromosome 7 May be caused by chromosomal translocation, inversion or rearrangement. Similar to this study, Grace E[ 7 ] found a patient with partial repetition of 7q22q32 with hypotonia, large ears, strabismus and other symptoms, Romain DR[ 8 ] found a patient with partial repetition of 7q22q31.2 with right kidney dysplasia, iron deficiency anemia, hearing impairment and other symptoms. Although the repeated cases of trisomy chromosome 7 have very severe clinical symptoms, the situation of case 2 is different, and the amplification of the 7q11.23q21.3 fragment of the fetus is the same as that of the mother at 4q31.3 position (see Fig. 2 c), considering that the mother has no clinical symptoms, the phenotype of the fetus is presumed to be normal, therefore, doctors recommend that pregnant women continue their pregnancy and have regular follow-up visits. When the gestational week was 29 weeks, ultrasound detected the fetus with a small range of ventricular septal defects (see Fig. 2 d), considering the possibility of automatic closure of the fetal ventricular septum, it was recommended that the pregnant woman give birth to a full-term child with normal development. When the fetus grew to 1 year and 4 months, ultrasound indicated that the ventricular septal defect reached 3-4mm. Doctors recommend to wait until the fetus is 3 years old to repair the ventricular septal defect. if the parents are carriers of balanced translocations, the probability of fetal chromosome structural imbalance is the highest [ 9 , 10 ], statistical analysis shows that the probability of fetal chromosome structural abnormality after prenatal diagnosis is 0.81%, among which the incidence of non-balanced mutual translocations is 0.13%[ 11 ], all three fetuses were imbalanced translocations and were aborted. The principle of balanced translocation to form unbalanced gametes may be that carriers of balanced translocation can form tetraceutes during meiosis, which can produce 36 kinds of gametes[ 12 ], of which one is normal gametes and one is balanced translocation gametes, and the tetraceutes formed can divide in a way of 2:2, 3:1, and 4:0, but the theoretical probability of producing normal gametes is not 1/36, Morel F[ 13 ] used Fish to analyze a pair of t(7; 8) For the gametes of brothers, it was found that the probabilities of para-segregation, O-1 separation, O-2 a separation, 3:1 separation and 4:0 separation in the gametes of older brothers were 56.7%, 25.1%, 11.1%, 7.06% and 0.04%, respectively, while the probabilities of corresponding gametes production in younger brothers were 62.84%, 17.61% and 12.8%, respectively. 6.47% and 0.28%, it can be seen that the probability of splitting according to 2:2 is much greater than that of splitting according to 3:1 and 4:0. The gametes of the pregnant woman in case 3 were obtained by ortho-2 a separation, the pregnant woman in case 4 is more special, it is the gametes produced under the condition of balanced translocation of three chromosomes, the gametes of the pregnant woman in case 5 were isolated in a 3:1 b manner. Case 3 was short arm deletion on chromosome 16 and long arm duplication on part of chromosome 18, related to this study, Al-Qattan MM[ 14 ] found that a boy with continuous deletion of SLX4, DNASE1, TRAP1 and CREBBP genes at 16p13.3 had a wide thumb with radial angulation, mild intellectual impairment, mild facial deformity and hydronephrosis were found in this case, and the CMA results of case 3 were basically consistent with the description of symptoms, the literature on 18q12.3q23 was rarely repeated, and no relevant studies were found. In case 4 , the short arm region of chromosome 20 was repeated at the long arm position of chromosome 9, there are few literatures on the amplification of 20p13p12.1, Li D[ 15 ] found that the CMA result of a laryngeal cancer patient was 20p13p12.1. Pachajoa H[ 16 ] found that a baby girl was diagnosed with right megaloureter 2 months after birth, and was diagnosed with mild mental retardation and slow cognitive rhythm at the age of 3, physical examination at the age of 17 revealed a round face, broad nose, xanthoxanoma of both lower eyelids, fold of inner canthus, long eyelid clefs, slow speech, poor coordination and thick hands, this case was partially consistent with the CMA results of Case 4 . Case 5 is a partial trisomy composed of the short arm region of chromosome 2 and the long arm region of chromosome 21, there are few studies on 2p25.3p22.2 duplication in the literature. Hu J[ 17 ] compared and characterized the genomic imbalance between primary and recurrent ovarian serous carcinoma, when determining genomic changes that can be used as prognostic markers, 2p22p25 repeats were found to be more common in highly recurrent ovarian serous carcinoma. Zhou L[ 18 ] found a case of 35.32 Mb repeats of 9p24.3-9p13.3 combined with 14.42 Mb repeats of 21q11.2-21q21.3, the patient mainly presented with craniofacial bone and finger abnormalities, short limbs, and varying degrees of mental impairment, Zhou L believed that the patient's symptoms were caused by the simultaneous repetition of 9p and 21q, but the patient's symptoms were consistent with the CMA chip results of case 5 , so it was suspected that the patient's symptoms were caused by 21q repetition or that 21q repetition had a greater effect. This study provides valuable experience for genetic counseling of fetuses with abnormal chromosome structure and reduces the possibility of forced abortion of fetuses with normal phenotype due to abnormal chromosome structure. However, this study can only reasonably predict the fetal phenotype, thereby reducing the generation of defective children, and cannot fully determine whether the fetal phenotype is normal, so there is a certain degree of uncertainty. G banding analysis technology and CMA combined detection of fetal chromosomes can not only find the complex structural abnormalities of the amniotic fluid chromosomes, but also determine whether the missing or repeated areas contain important genetic genes, then according to the results of the parents' chromosomes or the results of ultrasound examination, the abnormal situation of fetal chromosomes can be summarized and analyzed, so as to obtain scientific clinical advice. Declarations Data availability The data that support the findings of this study are available from the corresponding author, upon reasonable request. Funding Fund Project: The National Key Research and Development Program of China (2018YFC0114703). Author information Author details Medical Genetics, Zibo Maternal and Child Health Hospital, Zibo 255000, China. Authors ’ contributions LG, LY, SX, and MK analyzed and interpreted patient data. LG conducted the data collection and was a major contributor to the manuscript. The MK is responsible for conceiving and reviewing and editing the manuscript. All authors read and approved the final manuscript. Corresponding author Correspondence to Kai Mu Ethics declarations Ethics approval and consent to participate It has passed the review of Ethics Committee of Zibo Maternal and Child Health HospitalConsent for publication. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Acknowledgments The authors would like to thank the pregnant women and their babies who participated in the study, as well as the staff involved in prenatal diagnostic techniques(Yi Liu, Xuecheng Sun, Kai Mu). The author is grateful for the support of Zibo Maternal and Child Health Hospital and the support of China National Key Research and Development Program Fund. References Abarca-Barriga HH, Trubnykova M, Chavesta-Velásquez F, et al. Peruvian Newborn Male with 3p13 Deletion Syndrome Encompassing the FOXP1 Gene: Review of the Literature. J Pediatr Genet. 2020 Dec;9(4):270-278. Prontera P, Buldrini B, Aiello V, et al. Familial pericentric inversion of chromosome 18: intrafamilial variability of the recombinant dup(18q). Genet Couns. 2010;21(1):91-7. Popescu R, Grămescu M, Caba L, et al. A Case of Inherited t(4;10)(q26;q26.2) Chromosomal Translocation Elucidated by Multiple Chromosomal and Molecular Analyses[J]. Case Report and Review of the Literature. 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Chromosome 16p13.3 Contiguous Gene Deletion Syndrome including the SLX4, DNASE1, TRAP1, and CREBBP Genes Presenting as a Relatively Mild Rubinstein-Taybi Syndrome Phenotype: A Case Report of a Saudi Boy[J]. Case Rep Genet. 2020 Jan 9;2020:6143050. Li D, Wang X, Lu S, et al. Integrated analysis revealing genome-wide chromosomal copy number variation in supraglottic laryngeal squamous cell carcinoma[J]. Oncol Lett. 2020 Aug;20(2):1201-1212. Pachajoa H, Perafan L, Ramos I, Escobar ÁJ. Laparoscopic Hysterectomy and Bilateral Salpingectomy in a Patient with Microduplication Syndrome (20p13p12.1) and a Bicornuate Uterus: An Unreported Association[J]. Int J Womens Health. 2020 Aug 25;12:675-679. Hu J, Khanna V, Jones MW, Surti U. Comparative study of primary and recurrent ovarian serous carcinomas: comparative genomic hybridization analysis with a potential application for prognosis. Gynecol Oncol. 2003 Jun;89(3):369-75. Zhou L, Chen C, Zheng Z, et al. SNP array analysis of three cases with partial 21q trisomy[J]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2017 Dec 10;34(6):861-865. Chinese. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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 Advisory Board 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-4372185","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":300330531,"identity":"c955360b-ecc9-49c4-945d-046e6d994e00","order_by":0,"name":"Guojian Lv","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA00lEQVRIiWNgGAWjYBACNv7+759/VNjwsLE3HyBOC5/EATNmhjNpcvw8xxKI0yLHkGDGzNh22FhyRo4BkQ5jOJD2uLCNOXHDgZyPN94w2MnpNhDSwtxw3HjGOTaglrObLecwJBubHSBoy8EGCZ4ynsQNB3u3SfMwHEjcRlhLMoMED5tE4obDPM+I1ZLGJs3TZmAs2cbDRqQWiTPMhjPOJAADmc3Yco4BEX6R7+9hfPCh4j8Pm/zjhzfeVNjJEdSCAiR4iIwaZC2k6hgFo2AUjIIRAQCGcEGvxYto5AAAAABJRU5ErkJggg==","orcid":"","institution":"Medical Genetics, Zibo Maternal and Child Health Hospital, Zibo 255000, China.","correspondingAuthor":true,"prefix":"","firstName":"Guojian","middleName":"","lastName":"Lv","suffix":""},{"id":300330533,"identity":"2b63f7d9-a5d4-46d6-996f-8e02ac672ad1","order_by":1,"name":"Yi Liu","email":"","orcid":"","institution":"Medical Genetics, Zibo Maternal and Child Health Hospital, Zibo 255000, China.","correspondingAuthor":false,"prefix":"","firstName":"Yi","middleName":"","lastName":"Liu","suffix":""},{"id":300330536,"identity":"00d14b18-43ae-4ef6-a470-93e6b2a1065a","order_by":2,"name":"Xuecheng Sun","email":"","orcid":"","institution":"Medical Genetics, Zibo Maternal and Child Health Hospital, Zibo 255000, China.","correspondingAuthor":false,"prefix":"","firstName":"Xuecheng","middleName":"","lastName":"Sun","suffix":""},{"id":300330539,"identity":"c697a064-4cc9-4e25-82de-aab2a8ede339","order_by":3,"name":"Kai Mu","email":"","orcid":"","institution":"Medical Genetics, Zibo Maternal and Child Health Hospital, Zibo 255000, China.","correspondingAuthor":false,"prefix":"","firstName":"Kai","middleName":"","lastName":"Mu","suffix":""}],"badges":[],"createdAt":"2024-05-05 14:58:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4372185/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4372185/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":56477431,"identity":"08f165e1-3188-41a3-ad41-d578041b8029","added_by":"auto","created_at":"2024-05-14 17:47:19","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":650931,"visible":true,"origin":"","legend":"\u003cp\u003eCase 1: Fetal karyotype results, CMA results and fetal ultrasound images of pregnant woman in case 1\u003c/p\u003e\n\u003cp\u003eNote: a: The result of fetal karyotype in pregnant women's amniotic fluid was 46,Xn,inv(1)(p13q21),del(3)(p13p14), and the direction indicated by the arrow was inversion 1 and deletion 3. b: The CMA result of the pregnant amniotic fluid fetus was arr 3p14.2p12.3(62,450,296-79,586,304)x1. c: Ultrasound showed tetralogy of Fallot; d: ultrasound showed hydrocephalus.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4372185/v1/9b6f8f491419fa255c2d674f.png"},{"id":56477434,"identity":"1633bb7b-4e16-43c5-8c20-69e7f7313858","added_by":"auto","created_at":"2024-05-14 17:47:19","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":644812,"visible":true,"origin":"","legend":"\u003cp\u003eCase 2: Fetal karyotype results of amniotic fluid, CMA results, fish probe verification, and fetal ultrasound images in case 2.\u003c/p\u003e\n\u003cp\u003eNote: a: The result of fetal karyotype in maternal amniotic fluid was 46,Xn,der(4)ins(4; ?). (q31.3; ?). The direction indicated by the arrow was 7q11.23q21.3 amplification region. b: maternal amniotic fluid fetal CMA result was arr[hg19] 7q11.23q21.3(77,283,926-93,528,760)x3, c: ins(4; 7)→The chromosome indicated indicates that the repeated 7q11.23q21.3 fragment is inserted into the 4q31.1 position, resulting in a derived chromosome 4. d: Ultrasound showed the fetus with a ventricular septal defect.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4372185/v1/cf007caa31faaaf5d93f3a2b.png"},{"id":56477428,"identity":"40f84806-a60d-4a58-a363-69a27cf899ab","added_by":"auto","created_at":"2024-05-14 17:47:19","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":373734,"visible":true,"origin":"","legend":"\u003cp\u003eCase 3: Fetal karyotype and CMA results of amniotic fluid in pregnant women\u003c/p\u003e\n\u003cp\u003eNote: a: The results of fetal karyotype in maternal amniotic fluid were 46,Xn,der(16)t(16; 18) (p13.3; q12.3), the direction indicated by the arrow is chromosome 16 derived, b: The CMA result of maternal amniotic fluid fetus is arr[hg19] 16p13.3(85,880-1,256,722)x1,18q12.3q23(43,312,367-78,013,728)x3.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4372185/v1/b87618f134e34e2efaffdb6d.png"},{"id":56477433,"identity":"cb8c6806-64f9-46e1-8293-8da5121da37b","added_by":"auto","created_at":"2024-05-14 17:47:19","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":381614,"visible":true,"origin":"","legend":"\u003cp\u003eCase 4 Fetal karyotype and CMA results of amniotic fluid in pregnant women\u003c/p\u003e\n\u003cp\u003eNote: a: The results of fetal karyotype in maternal amniotic fluid were 46,Xn,der(9)t(9; 22. 20)(q12; p11; p12),der(22)t((9; 22. 20)mat, the directions indicated by the arrows were chromosome 9 and chromosome 22, respectively. b: The CMA result of pregnant women's amniotic fluid fetus was arr[hg19] 20p13PP12.1(61,661-13,722,351)x3.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-4372185/v1/68d8cb8ff0656a84c12ec219.png"},{"id":56477429,"identity":"d0c046a5-2eed-4c53-8517-a2a34dfa3b0c","added_by":"auto","created_at":"2024-05-14 17:47:19","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":459102,"visible":true,"origin":"","legend":"\u003cp\u003eCase 5 Fetal karyotype and CMA results of amniotic fluid in pregnant women\u003c/p\u003e\n\u003cp\u003eNote: a: The results of fetal karyotype in maternal amniotic fluid were 47,Xn,der(21)t(2; 21) (p22.2; q21.3),+21,; The arrow points to chromosome 21 derivative, b: The CMA result of maternal amniotic fluid fetus is arr[hg19] 2p25.3p22.2(12,770-37,352,776)x3,21q11.2q21.3(15,016,486-31,024,019)x3.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-4372185/v1/cc7f8d719ffb47a953692d61.png"},{"id":56477432,"identity":"9a95b7d2-101c-45f5-abbf-760d207d13ca","added_by":"auto","created_at":"2024-05-14 17:47:19","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":431752,"visible":true,"origin":"","legend":"\u003cp\u003eCase 6 Fetal karyotype and CMA results of amniotic fluid in pregnant women\u003c/p\u003e\n\u003cp\u003eNote: a: The result of fetal karyotype in pregnant women's amniotic fluid was 46,Xn,der(21)(18qter→18q12.3::21p13→21qter), and the direction indicated by the arrow was derived chromosome 21. b: Maternal amniotic fluid fetal CMA results were arr[hg19] 18q12.3q23(37,974,391-78,013,728)x3.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-4372185/v1/b192707f915ca513ee41fce9.png"},{"id":56477430,"identity":"ddaeaa3a-8d01-4e50-af03-727347cd4c63","added_by":"auto","created_at":"2024-05-14 17:47:19","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":438152,"visible":true,"origin":"","legend":"\u003cp\u003eCase 7 Fetal karyotype and CMA results of amniotic fluid in pregnant women\u003c/p\u003e\n\u003cp\u003eNote: a: The karyotype result of fetal amniotic fluid in pregnant women was 46,Xn,der(4)del(4)(q35.2)dup(4)(q35.2q26)dn, and the direction indicated by the arrow was chromosome 4 derived. b: The CMA results of pregnant women's amniotic fluid fetus were arr[GRCh37]4q26q35.2(116376542_188138856)x3, arr[GRCh37] 4q35.2(188155531_190957460)x1.\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-4372185/v1/ced64164e325831b01c9f49c.png"},{"id":56477427,"identity":"2a5e93b2-9788-4a48-8c96-f79911b20dc9","added_by":"auto","created_at":"2024-05-14 17:47:18","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":418925,"visible":true,"origin":"","legend":"\u003cp\u003eCase 8 Fetal karyotype and CMA results of amniotic fluid in pregnant women\u003c/p\u003e\n\u003cp\u003eNote: a: The karyotype result of fetal amniotic fluid in pregnant women was 46,X,der(X)del(X)(p22.31)dup(X)(p22.31p11.1)dn, and the direction indicated by the arrow was X-derived chromosome. b: The CMA result of pregnant women's amniotic fluid fetus was\u003c/p\u003e","description":"","filename":"8.png","url":"https://assets-eu.researchsquare.com/files/rs-4372185/v1/560d12a2df1ca74e0bfe49d1.png"},{"id":58998868,"identity":"40adc3f6-dfe9-4d8e-bdbe-2937ba0f1a96","added_by":"auto","created_at":"2024-06-25 06:53:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5686161,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4372185/v1/c8fa824a-6b37-4558-b8a5-0cdb8a27b1a7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prenatal diagnosis and counseling of fetal chromosomes with structural abnormalities","fulltext":[{"header":"Introduction","content":"\u003cp\u003eChromosome structure abnormality is one of the causes of fetal genetic diseases, with the development of society, the probability of fetal chromosome structure abnormality is gradually increasing, the combined application of ultrasound, chromosomal micoarray analysis (CMA), chromosome G banding analysis and fluorescence in situ hybridization(FISH) can significantly improve the probability of finding fetal chromosome structure abnormality, and play a role in the purpose of eugenics and fertility, and improve population quality.\u003c/p\u003e"},{"header":"Objects and methods","content":"\u003cdiv id=\"Sec3\"\u003e\n \u003ch2\u003e1.1 Research object\u003c/h2\u003e\n \u003cp\u003eFrom January 2012 to December 2023, 9867 pregnant women who came to our hospital for amniocentesis, pregnant women aged 17 to 55 years old, gestational weeks 15 to 35 weeks, due to advanced age, abnormal B-ultrasound, screening or non-invasive high risk of puncture, had been informed of the risk and signed informed consent before puncture.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\"\u003e\n \u003ch2\u003e1.2 Research method\u003c/h2\u003e\n \u003cp\u003e\u003cspan\u003eG banding analysis technology The sheep water obtained from the puncture was planted in two culture bottles and cultured in an incubator of 5% CO2 at 37℃ for 6\u0026ndash;8 days, the medium was changed from 8\u0026ndash;10 days, and colchicine was added for 10\u0026ndash;12 days to harvest, and the film was finally read after preparation, G-banding and Giemsa staining. According to the ISCN2020 edition, five karyotypes are analyzed, 20 numbers are counted, and if a chimera is encountered, 100 are added.\u003cbr\u003e\u003c/span\u003e \u003cspan\u003eChromosome microarray analysis The chip design analysis first selects the Affymetrix-based Cyto Scan 750K Array chip, according to the requirements in the operation manual provided by the American Affymetrix public test system, first carried out the amplification of the whole gene sequence, the detection and Analysis of markers and the scanning of the whole genome structure, and then carried out the copy number analysis of the whole genome with the Chromosome Analysis Suite software.\u003cbr\u003e\u003c/span\u003e \u003cspan\u003eFluorescence in situ hybridization analysis The three probes used in the FISH analysis were: 4p16.3(2,156,895-2,351,734), 7q21.12(86,802,721\u0026thinsp;\u0026minus;\u0026thinsp;86,97,97,95, 903) and 7p22.3(1,645,493-1,814,816). The metaphase division phase of each chromosome was analyzed by fluorescence microscope.\u003cbr\u003e\u003c/span\u003e \u003cspan\u003eUltrasound detection during fetal pregnancy Until the pregnant woman\u0026apos;s gestational age reached the appropriate time, ultrasound was used to detect the fetal double parietal diameter, fetal head circumference, heart, brain, kidney, and limbs development.\u003cbr\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n \u003ch2\u003e2.1 Fetal chromosome examination\u003c/h2\u003e\n \u003cp\u003eAmong the 9867 amniotic fluid chromosomes, 8 cases had complex structural abnormalities. Chromosome structural abnormalities in cases \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e, \u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e and \u003cspan class=\"InternalRef\"\u003e8\u003c/span\u003e came from new mutations (see Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, FIG. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003ea, FIG. 6a, FIG. 7a and FIG. 8a), chromosome structural abnormalities in case 2 came from their mothers (see Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and FIG. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003ea), chromosome structural abnormalities in cases \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e and \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e were due to the fact that their parents were balanced translocation carriers. It was followed by an unbalanced translocation (see Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, FIG 3a, 4a, 5a).\u003c/p\u003e\n \u003ch2\u003e2.2 Check on the fetal chip\u003c/h2\u003eThe CMA result of case \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e was that arr 3p14.2p12.3(62,450,296\u0026thinsp;\u0026minus;\u0026thinsp;79,586,304)x1, 3p14.2p12.3 had 16.34Mb deletion, which contained CADPS, SYNPR, SYNPR-AS1, FHIT, FOXP1 and other genes, there may be developmental delays, mental retardation, multiple deformities and other clinical symptoms (see Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eb). The CMA result of case 2 was arr[hg19] 7q11.23q21.3(77,283,926\u0026thinsp;\u0026minus;\u0026thinsp;93,528,760)x3, 7q11.23q21.3 with 15.5Mb amplification, including SEMA3A, FZD1, CACNA2D1, SLC25A40, SEMA3A, FZD1, CACNA2D1, and SLC25A40, there are 41 OMIM genes, including CYP51A1, SAMD9, which are related to brain neuron development, blood vessel and immune protein expression (see Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eb). The CMA results of case \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e were arr[hg19] 16p13.3(85,880-1,256,722)x1,18q12.3q23(43,312,367\u0026thinsp;\u0026minus;\u0026thinsp;78,013,728)x3, 16p13.3 with 1.17Mb fragment deletion, it contains 36 OMIM genes such as POLR3K, RHBDF1 and MPG, which can present clinical symptoms such as language and mental retardation, atrioventricular septal defect, facial morphological abnormalities, kidney enlargement, and wide thumb, there is 34.7Mb fragment amplification in 18q12.3q23, it contains 105 OMIM genes such as SLC14A1, EPG5, PSTPIP2, and so on, which may have mental retardation and low muscular tone symptoms (see Fig. 3b). CMA results of case \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e were as follows: arr[hg19] 20p13p12.1(61,661\u0026thinsp;\u0026minus;\u0026thinsp;13,722,351)x3, 20p13p12.1 had 13.66Mb fragment amplification, which contained 82 OMIM genes including SOX12, NRSN2, TRIB3 and RBCK1, patients may have developmental delays, mental retardation, language disorders, and broad nose (see Fig. 4b). The CMA results of case \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e were arr[hg19] 2p25.3p22.2(12,770\u0026thinsp;\u0026minus;\u0026thinsp;37,352,776)x3,21q11.2q21.3(15,016,486\u0026thinsp;\u0026minus;\u0026thinsp;31,024,019)x3, 2p25.3p22.2 had 37.34Mb of fragment repeats, it contains 82 OMIM genes such as SOX12, NRSN2, TRIB3, RBCK1, and so on, patients may show developmental delay, mental retardability, language disorder, broad nose bridge and other phenotypes, 21q11.2q21.3 has 16Mb fragment duplication, covering the Early-onset_Alzheimer_disease_with_cerebral_amyloid_angiopathy region and containing 31 OMIM genes such as LIPI, APP, ABCC13 and HSPA13, symptoms of abnormal finger morphology, mental retardation, and developmental delay may occur (see Fig. 5b). The CMA result of case \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e was arr[hg19] 18q12.3q23(37,974,391\u0026thinsp;\u0026minus;\u0026thinsp;78,013,728)x3, and there were 40.039Mb replicates in the 18q12.3q23 region, which contained 115 OMIM genes such as PIK3C3, RIT2, SYT4 and SETBP1, symptoms such as stunting, mental retardation, short stature and enlarged heart may occur (Fig. 6b). The CMA results of case \u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e were arr[GRCh37]4q26q35.2(116376542_188138856)x3, arr[GRCh37] 4q35.2(188155531_190957460)x1, 4q26q35.2 with 71.762Mb replicates, it contains 179 OMIM genes, including TRAM1L1, NDST3, PRSS12, and so on, which may cause intellectual disability, comprehensive developmental delay, autism, and so on, there is 2.802Mb deletion in the 4q35.2 region, including 3 OMIM genes ZFP42, FRG1, FRG2, this segment had no pathogenic significance (Fig. 7b). The CMA results of case \u003cspan class=\"InternalRef\"\u003e8\u003c/span\u003e were arr[GRCh37] Xp22.31p11.1(9041083_58455353)x3, arr[GRCh37] Xp22.33p22.31(168552_9040480)x1, there were 49.414Mb repeats in Xp22.31p11.1 region, including 268 OMIM genes such as TBL1X, GPR143, SHROOM2, CLCN4,and so on, and 8.872Mb deletion in Xp22.33p22.31 region, it contains 43 OMIM genes, including PLCXD1, GTPBP6, PPP2R3B, and SHOX, which can cause symptoms such as global stunting, ichthyosis, and short stature (see Fig. 8b).\u003cp\u003e2.3 \u003cstrong\u003eVerification of Fish probe\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eFigure \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003ec shows that the red fluorescence represents 7p22.3(1,645,493-1,814,816), orange fluorescence represents 7q21.12(86,802,721\u0026thinsp;\u0026minus;\u0026thinsp;86,97,97,95,95,903), the green fluorescence represents 4p16.3(2,156,895-2,351,734), ins(4; 7)\u0026rarr; The chromosome indicated indicates that the repeated 7q11.23q21.3 fragment is inserted into the 4q31.1 position, resulting in a derived chromosome 4.\u003c/p\u003e\n \u003cp\u003e2.4 \u003cstrong\u003eFetal ultrasound detection during pregnancy\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eIn case \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, ultrasound examination showed multiple deformities of the fetus, which were consistent with tetralogy of Fallot, hydrocephalus, and double renal dysplasia (see Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003ec, \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003ed). In case 2, the fetal ventricular septal defect was detected by ultrasound (see Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003ed). In other cases, no abnormality was detected by ultrasound before abortion.\u0026nbsp;\u003c/p\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eAmniotic fluid karyotype and chip detection\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003ecase\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\"\u003eClinical indication\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\"\u003eFetal karyotype\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\"\u003eParental karyotype\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\"\u003eCMA\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\"\u003eending\u003cbr\u003e\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e1\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eHusband karyotype 46,XY,inv(1)(p13q21)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e46,Xn,inv(1)(p13q21),del(3)(p13p14)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003ePaternal karyotype: 46,XY,inv(1)(p13q21); The mother\u0026apos;s karyotype was normal\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003edel(3)(p12.3p14.2) is missing 16.34Mb\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eInduction of Labour\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e2\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eNIPT shows a 15.54Mb duplication in 7q21.11-q21.3\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e46,Xn,der(4)ins(4;?)(q31.3;?)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eFather karyotype normal, mother: 46,XX,der(4)ins(4; ?). (q31.3; ?).\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003edup(7)(q11.23q21.3) repeat 15.5Mb\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eeutocia\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e3\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eNIPT shows high risk on chromosome 18\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e46,Xn,der(16)t(16;18)(p13.3;q12.3)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eFather karyotype normal, mother: 46,XX,t(16; 18) (p13.3; Q12.3)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003edel(16)(p13.3)missing1.17Mb;dup(18)(q12.3q23) repeat 34.7Mb\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eInduction of Labour\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e4\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003ePregnant women have 46,XX,t(9; 22. 20)(q12; p11; p12)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e46,Xn,der(9)t(9;22;20)(q12;p11;p12),der(22)t((9;22;20)mat\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eFather karyotype normal, mother: 46,XX,t(9; 22. 20)(q12; p11; p12)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003edup(20)(p12.1p13) repeat 13.66Mb\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eInduction of Labour\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e5\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eNIPT shows high risk of chromosome 21\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e47,Xn,der(21 )t(2;21)(p22.2;q21.3),+21\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eFather karyotype normal, mother: 46,XX,t(2; 21) (p22.2; Q21.3)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003edup(2)(p22.2p25.3) repeat 37.34Mb; dup(21)(q11.2q21.3) repeat 16Mb\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eInduction of Labour\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e6\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eDown\u0026apos;s screening for chromosome 21 is high-risk\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e46,Xn,der(21)(18qter\u0026rarr;18q12.3::21p13\u0026rarr;21qter)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eThe father\u0026apos;s karyotype was normal; The mother\u0026apos;s karyotype was normal\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003edup(18)(q12.3q23) repeat 40.039Mb\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eInduction of Labour\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e7\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eColor ultrasound hint: NT thickening old age\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e46,Xn,der(4)del(4)(q35.2)dup(4)(q35.2q26)dn\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eThe father\u0026apos;s karyotype was normal; The mother\u0026apos;s karyotype was normal\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003edup(4)(q26q35.2) repeat 71.762Mb; del(4)(q35.2) is missing 2.802Mb\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eInduction of Labour\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e8\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eNIPT showed fewer sex chromosomes\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e46,X,der(X)del(X)(p22.31)dup(X)(p22.31p11.1)dn\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eThe father\u0026apos;s karyotype was normal; The mother\u0026apos;s karyotype was normal\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003edup(X)(p11.1p22.31) repeat 49.414Mb; del(X)(p22.31p22.33) is missing 8.872Mb\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eInduction of Labour\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Comment","content":"\u003cp\u003eIt is known that fetal chromosome structural abnormalities generally have three sources, one is a new mutation, one is directly from the parents, and one is because the parents are carriers of balanced translocation, the fetus is unbalanced translocation. Fetal chromosomal structural abnormalities in cases \u003cspan\u003e1\u003c/span\u003e, \u003cspan\u003e6\u003c/span\u003e, \u003cspan\u003e7\u003c/span\u003e, and \u003cspan\u003e8\u003c/span\u003e were new mutations, and labor had been induced. In case 2, the fetal chromosomal structural abnormality originated from the mother and was currently delivered vaginally. The structural abnormalities of fetal chromosomes in cases \u003cspan\u003e3\u003c/span\u003e, \u003cspan\u003e4\u003c/span\u003e, and \u003cspan\u003e5\u003c/span\u003e were due to the fact that their parents were carriers of balanced translocation, resulting in three cases of unbalanced fetal chromosome translocation, which have been aborted.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase 1\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ein this study was deletion of copy number in the short arm of chromosome 3, similar to this study, Abarca-Barriga HH[\u003cspan\u003e1\u003c/span\u003e] found that a Peruvian newborn identified as 3p13p14.1 lost 5.5Mb copy number variation, its clinical symptoms include prolonged eye distance, iridia, microphthalmia, high palate, neurosensory deafness, heart malformation, developmental delay, seizures and nostril atresia, and so on, and the above symptoms are believed to be caused by the deletion of 54 genes such as FOXP1, UBA3, FAM19A1 and MITF, and the missing genes in case \u003cspan\u003e1\u003c/span\u003e completely cover these 54 genes, the symptoms of multiple deformities and developmental delays predicted by CMA were basically consistent with the above Peruvian newborns. Case \u003cspan\u003e6\u003c/span\u003e in this study was a duplication of the long arm part of chromosome 18, similar to this study, Prontera P[\u003cspan\u003e2\u003c/span\u003e] found that in a family, a mother and a husband and wife both carried rec dup (18q), showing deformities and short stature, but only the son had symptoms of mild mental retardation and language retardation, this is similar to the CMA prediction of case \u003cspan\u003e6\u003c/span\u003e, which may show symptoms such as developmental delay, intellectual impairment, and short stature. In this study, case \u003cspan\u003e7\u003c/span\u003e had both deletion and duplication of the long arm of chromosome 4. Popescu R[\u003cspan\u003e3\u003c/span\u003e] found that a boy had duplication of chromosome 4 in the same region as case \u003cspan\u003e7\u003c/span\u003e, and its clinical characteristics were as follows: flattened occipital region, Slight turbidity, A high, broad forehead, Long eye distance, Deep eyes, Downward-sloping and short palpebral fissure, Epicanthus, Nose protruding, base wide, bulbous tip, Small mouth, Small posterior jaw, large short middle jaw, with prominent relief, Low, protruding ears, the CMA prediction of congenital heart disease was very different from that of case \u003cspan\u003e7\u003c/span\u003e. The Xp22.31p11.1(9041083_58455353) repeat region of case \u003cspan\u003e8\u003c/span\u003e completely covers multiple dose-response regions and dose-response genes, such as the NR0B1 gene included in the Xp21.2 region, which is considered to be a candidate gene involved in XY gonadal hypoplasia if overexpressed[\u003cspan\u003e4\u003c/span\u003e], for example, in the study of repetition area p11.23-p11.22, Verbeek S[\u003cspan\u003e5\u003c/span\u003e] found that a 13-year-old girl suffered from Xp11.22-p11.23 repetition syndrome, and she presented with severe non-paranoplastic Lambert-Eaton myasthenia syndrome (LEMS). Another missing fragment Xp22.33p22.31(168552_9040480) in case \u003cspan\u003e8\u003c/span\u003e was found by Yin T[\u003cspan\u003e6\u003c/span\u003e] in a related study, the CMA test results of a 19-month-old boy indicated that about 8.3Mb fragments of Xp22.33p22.31 were missing, Yq11.221-qter had about 43.3Mb fragment repeats, and its clinical symptoms were short stature, nasal root invagement, bilateral cryptorchidism, and mental retardency. The boy\u0026apos;s symptoms were mainly related to the absence of Xp, which was partially consistent with the CMA results of case \u003cspan\u003e8\u003c/span\u003e.\u003c/p\u003e\n\u003cp\u003eIn case 2, the region of the long arm of chromosome 7 is repeated at the long arm position of chromosome 4. The cause of trisomy of the long arm part of chromosome 7 May be caused by chromosomal translocation, inversion or rearrangement. Similar to this study, Grace E[\u003cspan\u003e7\u003c/span\u003e] found a patient with partial repetition of 7q22q32 with hypotonia, large ears, strabismus and other symptoms, Romain DR[\u003cspan\u003e8\u003c/span\u003e] found a patient with partial repetition of 7q22q31.2 with right kidney dysplasia, iron deficiency anemia, hearing impairment and other symptoms. Although the repeated cases of trisomy chromosome 7 have very severe clinical symptoms, the situation of case 2 is different, and the amplification of the 7q11.23q21.3 fragment of the fetus is the same as that of the mother at 4q31.3 position (see Fig. \u003cspan\u003e2\u003c/span\u003ec), considering that the mother has no clinical symptoms, the phenotype of the fetus is presumed to be normal, therefore, doctors recommend that pregnant women continue their pregnancy and have regular follow-up visits. When the gestational week was 29 weeks, ultrasound detected the fetus with a small range of ventricular septal defects (see Fig. \u003cspan\u003e2\u003c/span\u003ed), considering the possibility of automatic closure of the fetal ventricular septum, it was recommended that the pregnant woman give birth to a full-term child with normal development. When the fetus grew to 1 year and 4 months, ultrasound indicated that the ventricular septal defect reached 3-4mm. Doctors recommend to wait until the fetus is 3 years old to repair the ventricular septal defect.\u003c/p\u003e\n\u003cp\u003eif the parents are carriers of balanced translocations, the probability of fetal chromosome structural imbalance is the highest [\u003cspan\u003e9\u003c/span\u003e, \u003cspan\u003e10\u003c/span\u003e], statistical analysis shows that the probability of fetal chromosome structural abnormality after prenatal diagnosis is 0.81%, among which the incidence of non-balanced mutual translocations is 0.13%[\u003cspan\u003e11\u003c/span\u003e], all three fetuses were imbalanced translocations and were aborted. The principle of balanced translocation to form unbalanced gametes may be that carriers of balanced translocation can form tetraceutes during meiosis, which can produce 36 kinds of gametes[\u003cspan\u003e12\u003c/span\u003e], of which one is normal gametes and one is balanced translocation gametes, and the tetraceutes formed can divide in a way of 2:2, 3:1, and 4:0, but the theoretical probability of producing normal gametes is not 1/36, Morel F[\u003cspan\u003e13\u003c/span\u003e] used Fish to analyze a pair of t(7; 8) For the gametes of brothers, it was found that the probabilities of para-segregation, O-1 separation, O-2\u003csup\u003ea\u003c/sup\u003e separation, 3:1 separation and 4:0 separation in the gametes of older brothers were 56.7%, 25.1%, 11.1%, 7.06% and 0.04%, respectively, while the probabilities of corresponding gametes production in younger brothers were 62.84%, 17.61% and 12.8%, respectively. 6.47% and 0.28%, it can be seen that the probability of splitting according to 2:2 is much greater than that of splitting according to 3:1 and 4:0. The gametes of the pregnant woman in case \u003cspan\u003e3\u003c/span\u003e were obtained by ortho-2\u003csup\u003ea\u003c/sup\u003e separation, the pregnant woman in case \u003cspan\u003e4\u003c/span\u003e is more special, it is the gametes produced under the condition of balanced translocation of three chromosomes, the gametes of the pregnant woman in case \u003cspan\u003e5\u003c/span\u003e were isolated in a 3:1\u003csup\u003eb\u003c/sup\u003e manner. Case \u003cspan\u003e3\u003c/span\u003e was short arm deletion on chromosome 16 and long arm duplication on part of chromosome 18, related to this study, Al-Qattan MM[\u003cspan\u003e14\u003c/span\u003e] found that a boy with continuous deletion of SLX4, DNASE1, TRAP1 and CREBBP genes at 16p13.3 had a wide thumb with radial angulation, mild intellectual impairment, mild facial deformity and hydronephrosis were found in this case, and the CMA results of case \u003cspan\u003e3\u003c/span\u003e were basically consistent with the description of symptoms, the literature on 18q12.3q23 was rarely repeated, and no relevant studies were found. In case \u003cspan\u003e4\u003c/span\u003e, the short arm region of chromosome 20 was repeated at the long arm position of chromosome 9, there are few literatures on the amplification of 20p13p12.1, Li D[\u003cspan\u003e15\u003c/span\u003e] found that the CMA result of a laryngeal cancer patient was 20p13p12.1. Pachajoa H[\u003cspan\u003e16\u003c/span\u003e] found that a baby girl was diagnosed with right megaloureter 2 months after birth, and was diagnosed with mild mental retardation and slow cognitive rhythm at the age of 3, physical examination at the age of 17 revealed a round face, broad nose, xanthoxanoma of both lower eyelids, fold of inner canthus, long eyelid clefs, slow speech, poor coordination and thick hands, this case was partially consistent with the CMA results of Case \u003cspan\u003e4\u003c/span\u003e. Case \u003cspan\u003e5\u003c/span\u003e is a partial trisomy composed of the short arm region of chromosome 2 and the long arm region of chromosome 21, there are few studies on 2p25.3p22.2 duplication in the literature. Hu J[\u003cspan\u003e17\u003c/span\u003e] compared and characterized the genomic imbalance between primary and recurrent ovarian serous carcinoma, when determining genomic changes that can be used as prognostic markers, 2p22p25 repeats were found to be more common in highly recurrent ovarian serous carcinoma. Zhou L[\u003cspan\u003e18\u003c/span\u003e] found a case of 35.32 Mb repeats of 9p24.3-9p13.3 combined with 14.42 Mb repeats of 21q11.2-21q21.3, the patient mainly presented with craniofacial bone and finger abnormalities, short limbs, and varying degrees of mental impairment, Zhou L believed that the patient\u0026apos;s symptoms were caused by the simultaneous repetition of 9p and 21q, but the patient\u0026apos;s symptoms were consistent with the CMA chip results of case \u003cspan\u003e5\u003c/span\u003e, so it was suspected that the patient\u0026apos;s symptoms were caused by 21q repetition or that 21q repetition had a greater effect.\u003c/p\u003e\n\u003cp\u003eThis study provides valuable experience for genetic counseling of fetuses with abnormal chromosome structure and reduces the possibility of forced abortion of fetuses with normal phenotype due to abnormal chromosome structure. However, this study can only reasonably predict the fetal phenotype, thereby reducing the generation of defective children, and cannot fully determine whether the fetal phenotype is normal, so there is a certain degree of uncertainty.\u003c/p\u003e\n\u003cp\u003eG banding analysis technology and CMA combined detection of fetal chromosomes can not only find the complex structural abnormalities of the amniotic fluid chromosomes, but also determine whether the missing or repeated areas contain important genetic genes, then according to the results of the parents\u0026apos; chromosomes or the results of ultrasound examination, the abnormal situation of fetal chromosomes can be summarized and analyzed, so as to obtain scientific clinical advice.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author, upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFund Project: The National Key Research and Development Program of China \u0026nbsp; \u0026nbsp;(2018YFC0114703).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMedical Genetics, Zibo Maternal and Child Health Hospital, Zibo 255000, China.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u003c/strong\u003e\u003cstrong\u003e\u0026rsquo;\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003econtributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLG, LY, SX, and MK analyzed and interpreted patient data. LG conducted the data collection and was a major contributor to the manuscript. The MK is responsible for conceiving and reviewing and editing the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorresponding author\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCorrespondence to\u0026nbsp;Kai Mu\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIt has passed the review of Ethics Committee of Zibo Maternal and Child Health HospitalConsent for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank the pregnant women and their babies who participated in the study, as well as the staff involved in prenatal diagnostic techniques(Yi Liu, Xuecheng Sun, Kai Mu). The author is grateful for the support of Zibo Maternal and Child Health Hospital and the support of China National Key Research and Development Program Fund.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAbarca-Barriga HH, Trubnykova M, Chavesta-Vel\u0026aacute;squez F, et al. Peruvian Newborn Male with 3p13 Deletion Syndrome Encompassing the FOXP1 Gene: Review of the Literature. J Pediatr Genet. 2020 Dec;9(4):270-278.\u003c/li\u003e\n\u003cli\u003eProntera P, Buldrini B, Aiello V, et al. Familial pericentric inversion of chromosome 18: intrafamilial variability of the recombinant dup(18q). Genet Couns. 2010;21(1):91-7.\u003c/li\u003e\n\u003cli\u003ePopescu R, Grămescu M, Caba L, et al. A Case of Inherited t(4;10)(q26;q26.2) Chromosomal Translocation Elucidated by Multiple Chromosomal and Molecular Analyses[J]. Case Report and Review of the Literature. Genes (Basel). 2021 Dec 7;12(12):1957.\u003c/li\u003e\n\u003cli\u003eFrancese-Santos AP, Meinel JA, Piveta CSC, et al. A Novel Look at Dosage-Sensitive Sex Locus Xp21.2 in a Case of 46,XY Partial Gonadal Dysgenesis without NR0B1 Duplication. Int J Mol Sci. 2022 Dec 28;24(1):494. \u003c/li\u003e\n\u003cli\u003eVerbeek S, Vanakker O, Mercelis R, et al. Lambert-Eaton myasthenic syndrome in a 13-year-old girl with Xp11.22-p11.23 duplication. Eur J Paediatr Neurol. 2014 May;18(3):439-43.\u003c/li\u003e\n\u003cli\u003eYin T, Wang Y, Wang Z, Zhang R, Wang L. [Genetic study of a child carrying a maternally derived unbalanced 46,Y,der(X)t(X;Y)(p22;q11) chromosomal translocation]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2021 Apr 10;38(4):376-379. Chinese.\u003c/li\u003e\n\u003cli\u003eGrace E, Sutherland GR, Bain AD. Familial insertional translocation. Lancet. 1972 Jul 29;2(7770):231.\u003c/li\u003e\n\u003cli\u003eRomain DR, Cairney H, Stewart D, et al. Three cases of partial trisomy 7q owing to rare structural rearrangements of chromosome 7. J Med Genet. 1990 Feb;27(2):109-13.\u003c/li\u003e\n\u003cli\u003eLuo Xiaojin, Guo Biyun, Hu Liang et al. Prenatal diagnosis of nonequilibrium chromosomal translocation in the second trimester of pregnancy [J]. Journal of Practical Medicine, 2016, 32(15): 2483-2485. (in Chinese)\u003c/li\u003e\n\u003cli\u003eWesterfield L, Darilek S, van den Veyver IB. Counseling Challenges with Variants of Uncertain Significance and Incidental Findings in Prenatal Genetic Screening and Diagnosis[J]. J Clin Med. 2014 Sep 12;3(3):1018-32.\u003c/li\u003e\n\u003cli\u003eWellesley D, Dolk H, Boyd PA, et al. Rare chromosome abnormalities, prevalence and prenatal diagnosis rates from population-based congenital anomaly registers in Europe[J]. Eur J Hum Genet.2012 May;20(5):521-6.\u003c/li\u003e\n\u003cli\u003eWang H. Theoretical analysis of gamete types in carriers of two chromosome balanced translocations [J]. 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Laparoscopic Hysterectomy and Bilateral Salpingectomy in a Patient with Microduplication Syndrome (20p13p12.1) and a Bicornuate Uterus: An Unreported Association[J]. Int J Womens Health. 2020 Aug 25;12:675-679. \u003c/li\u003e\n\u003cli\u003eHu J, Khanna V, Jones MW, Surti U. Comparative study of primary and recurrent ovarian serous carcinomas: comparative genomic hybridization analysis with a potential application for prognosis. Gynecol Oncol. 2003 Jun;89(3):369-75.\u003c/li\u003e\n\u003cli\u003eZhou L, Chen C, Zheng Z, et al. SNP array analysis of three cases with partial 21q trisomy[J]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2017 Dec 10;34(6):861-865. Chinese.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Fetal chromosome structure abnormalities, G banding analysis, CMA, FISH","lastPublishedDoi":"10.21203/rs.3.rs-4372185/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4372185/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjectives\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo explore the pregnancy, fertility risk and genetic suggestions of pregnant women with complex structural abnormalities of fetal chromosomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmniotic fluid puncture, chromosome culture of amniotic fluid and chromosome G banding analysis were performed on 9867 pregnant women who came to our hospital for prenatal diagnosis from 2012 to 2023, CMA was performed in 8 pregnant women with complex structural abnormalities in amniotic fluid.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eChromosome G banding analysis showed that the karyotypes of all 8 cases were structural abnormalities, with deletion and duplication, combined with CMA results, comprehensive analysis showed that case 1 was derived chromosome 3 with deletionof 3p13p14. In case 2, 7q11.23q21.3 was inserted at 4q31.3. Case 3 was derived chromosom 16 with deletion of 16p13.3 and duplication of 18q12.3q23. Case 4 was derived chromosome 9 with duplication of 20p12.1p13. Case 5 was derived chromosome 21 with duplication of 2p22.2p25.3 and 21q11.2q21.3. Case 6 was derived chromosome21 with duplication of 18q12.3q23; Case 7 was derived chromosome 4 with duplication of 4q26q35.2(116376542_188138856) and deletion of 4q35.2(188155531_190957460), and case 8 was derived chromosome X with duplication of Xp22.31p11.1(9041083_58455353) and deletion of Xp22.33p22.31(168552_9040480).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe combination of G-banding analysis technology and CMA can not only detect the complex structural abnormalities of the amniotic fluid chromosomes, but also determine whether the missing or repeated regions contain important genetic genes. Then, by referring to the results of the parents' chromosomes or the results of ultrasound examination, the abnormalities of fetal chromosomes are summarized and analyzed, so as to obtain clinical consultation opinions.\u003c/p\u003e","manuscriptTitle":"Prenatal diagnosis and counseling of fetal chromosomes with structural abnormalities","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-14 17:47:12","doi":"10.21203/rs.3.rs-4372185/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c7b326a4-18d9-4903-935f-6acf51ce0d73","owner":[],"postedDate":"May 14th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-25T06:45:09+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-14 17:47:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4372185","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4372185","identity":"rs-4372185","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}