Proximal 4p Deletion Syndrome in a Woman With Developmental Delay: A Case Report and Literature Review

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While WHS, associated with distal deletions, has well-characterized phenotypic features, proximal 4p deletion syndrome, involving the 4p14-p 16.1 region, shows milder manifestations, and its causative gene remains unknown with fewer reported cases. Here we report a Chinese case: a 21-year-old female with a peripheral blood chromosomal karyotype of 46,XX,del(4)(p15.3-p16). NGS-CNVA further revealed an 11.7 Mb deletion in the 4p16.2-p15.32 region and a 1.25 Mb microduplication in 16p13.13. She had ovarian dysfunction, and mild mental retardation without typical proximal 4p deletion phenotypes. Through analysis of Genecards and OMIM databases, we identified two genesneurodevelopmental genes DRD5 and WFS1, and four ovarian dysfunction-related genes WFS1, CC2D2A, PROM1, and QDPR, suggesting their roles in the patient's manifestations. Additionally, a review of 38 published cases of proximal 4p deletion syndrome revealed 21 cases with an overlap in the deleted region with our case. This report not only enhances the recognition of this rare syndrome among clinicians but also provides a basis for further exploration of the potential causative genes, contributing to a better understanding of the genotype-phenotype correlations in proximal 4p deletion syndrome. 4p15.32-16.2 interstitial deletion 16p13.13 duplication mental retardation ovarian dysfunction Figures Figure 1 Figure 2 Figure 3 Introduction Chromosomal deletions involving the short arm of chromosome 4 (4p) have been associated with two distinct clinical phenotypes: Wolf-Hirschhorn syndrome (WHS) and proximal 4p deletion syndrome. WHS, primarily caused by distal deletions in the 4p16.3-pter region, is characterized by distinctive craniofacial dysmorphology (e.g., trigonocephaly, broad nasal bridge, and hypoplastic nasal alae), severe developmental delay, and intellectual disability [1,2]. In contrast, proximal 4p deletion syndrome, defined by deletions in the 4p14-p16.1 region, presents with milder clinical manifestations, including mild to moderate intellectual disability, subtle dysmorphic features (e.g., long face, up-slanting palpebral fissures, epicanthal folds, and large lips), and skeletal abnormalities (e.g., pectus excavatum, genuvalga, and joint hyperlaxity) [3,4]. Despite increasing reports of proximal 4p deletions, the syndrome remains understudied, with approximately 37 cases documented in the literature [5]. Most prior studies relied on conventional karyotyping, limiting the precision of deletion mapping; only a subset of cases have been characterized using high-resolution genomic techniques [6–9]. The molecular basis of proximal 4p deletion syndrome remains unclear, as causative genes have not been definitively identified. Notably, phenotypic variability among reported cases further complicates research. While some patients exhibit classic features like developmental delay and dysmorphology, others present with atypical manifestations [10,11]. Here, we described the first Chinese case of proximal 4p deletion syndrome, characterized by an 11.7 Mb deletion in 4p15.32-p16.2 and a 1.25 Mb microduplication in 16p13.13. The patient presented with ovarian dysfunction, and mild intellectual disability, lacking typical craniofacial features of proximal 4p deletion syndrome. Through genomic database analysis (Genecards and OMIM), we identified candidate genes (e.g., WFS1, DRD5, CC2D2A, PROM1and QDPR) that may contribute to her phenotypes. Furthermore, a systematic review of 38 published cases revealed 20 with overlapping deletion regions, enabling comparative analysis of genotype-phenotype associations. This report aims to: (1) expand the clinical and genetic spectrum of proximal 4p deletion syndrome, (2)provide new insights into potential causative genes, advancing our understanding of this rare syndrome. We hope this report will help make this syndrome more recognizable among clinicians and provide a foundation for identifying the primary causative gene. Patient presentation The proband was a 21-year-old female, who presented to our outpatient service due to primary infertility and ovarian dysfunction. The patient had a history of mental retardation, diagnosed as "Intellectual Disability Level 3." She was able to perform basic activities of daily living, including walking, personal hygiene, and feeding herself. Her medical history revealed that she attained menarche at the age of 13 and had regular menstrual cycles. On physical examination, the patient exhibited normal vital signs and systemic functions. Her external genitalia appeared normal, and she had a normal-sized cervix. Transthoracic echocardiography revealed no abnormalities. Laboratory investigations, including routine blood parameters, liver and kidney function tests, myocardial enzymes, blood coagulation profile, thyroid hormones (TH), Human Growth Hormone, ACTH, and sex hormones, were within normal limits. There was no history of seizures according to her parents. The patient presented with a tall and thin body habitus but lacked minor dysmorphic features associated with proximal 4p deletion syndrome. The patient did not undergo specific therapeutic interventions related to her chromosomal abnormality. However, she was counseled regarding the potential implications of her condition on fertility and reproductive health. The proband also had a sister and a brother, who were healthy, but their karyotypes were unavailable. The patient's parents were healthy and did not undergo routine chromosomal analysis. Results Routine chromosomal analysis using standard G banding revealed a deletion of the short arm of chromosome 4, designated as 46, XX, del(4)(p15.3-p16) (Fig. 1 ). Subsequent NGS-CNVA testing on the patient's genomic DNA showed an approximately 11.7 Mb deletion in the 4p15.32-p16.2 region (chr4:g.5776037_17548280del) and an approximately 1.25 Mb duplication in the 16p13.13 region (chr16:g.11263062_12513616dup) (Fig. 2 ). A total of 101 genes were deleted in the affected region. Additionally, 19 genes were identified in the duplicated region. A total of 498 genes related to neurodevelopment and 2206 genes related to ovarian dysfunction were collected from the GeneCards and OMIM databases after combining and deleting repetitive genes. The intersection between the genes related to neurodevelopment and ovarian dysfunction and the deleted genes in our case was then identified, serving as potential genes for causal genes. Ultimately, 2 overlapping genes, including WFS1 and DRD5, for the neurodevelopment(Fig. 3 A) and 4 ovarian dysfunction-related genes(Fig. 3 B), including WFS1, CC2D2A, PROM1 and QDPR, were identified. A review of the literature revealed 37 (Supplementary tabl e1 )reported cases of proximal 4p deletion syndrome, with 19 cases(Table 1) exhibiting an overlap with the deleted region in our patient's case. Materials and Methods Cytogenetic analysis Peripheral blood was cultured and harvested using standard cytogenetic protocols. Chromosomal preparations were made using the G-banding technique, which has a resolution between 300 and 400 bands. Twenty metaphase cells were analyzed to determine the chromosomal karyotypes, following the guidelines of the International System of Human Cytogenetic Nomenclature (ISCN2016). NGS-CNV analysis In addition, NGS-CNV was performed on the proband's genomic DNA, which was extracted from PBMCs. This analysis was carried out using the NovaSeq 6000 platform from Illumina, based in San Diego, CA, United States. Acquisition of Related Genes Neurodevelopment-related genes and ovarian dysfunction related genes were downloaded from databases such as Genecards and OMIM. A Venn diagram was generated using the R 4.4.2 software with R package(ggvenn). DISCUSSION This study describes a first Chinese patient with an 11.7 Mb deletion in 4p15.32-p16.2 and a 1.25 Mb duplication in 16p13.13, presenting with ovarian dysfunction, mild intellectual disability and tall and thin habitus. Classical proximal 4p deletion syndrome, typically caused by deletions involving the 4p16.1-p14 region, is characterized by mild-to-moderate intellectual disability, subtle craniofacial dysmorphisms (e.g., long face, up-slanting palpebral fissures), and skeletal abnormalities (e.g., pectus excavatum, joint hyperlaxity) [12–13]. Notably, the critical region underlying these classic phenotypes has been suggested to 4p15.2–15.33: a literature review of 19 cases demonstrated that larger deletions extending into 4p15.2–15.33 more frequently result in craniofacial dysmorphisms and skeletal abnormalities, presumably due to the disruption of a broader repertoire of genes [14–16]. In contrast, our patient presented with only moderate intellectual disability without the aforementioned classic features; instead, she exhibited ovarian dysfunction, a manifestation not previously linked to proximal 4p deletions. This phenotypic discrepancy is attributable to the unique deletion interval in our case: a relatively small (11.7 Mb) deletion restricted to 4p15.32-p16.2, which spares most of the 4p15.2–15.33 critical region. Preservation of this critical region likely retained key genes governing craniofacial and skeletal development, thereby avoiding dysmorphic features. Importantly, the deleted interval still encompasses genes associated with cognitive function, which likely underpin the observed moderate intellectual disability.​Collectively, these observations highlight that the phenotypic spectrum of proximal 4p deletion syndrome is shaped by both the size of the deletion and the specificity of the involved interval—with disruption of the 4p15.2–15.33 critical region being central to the manifestation of classic craniofacial and skeletal abnormalities. Through integration of database analysis (GeneCards, OMIM), we identified several candidate genes within the 4p deletion interval that may drive the observed phenotypes. The patient’s mild intellectual disability (Level 3) aligns with the syndrome’s core feature. Among the deleted genes, WFS1 and DRD5 are strong candidates. WFS1 (Wolfram syndrome 1) encodes a transmembrane protein critical for neurodevelopment and endoplasmic reticulum homeostasis; loss-of-function mutations cause Wolfram syndrome, characterized by intellectual disability and neurodegeneration [17]. DRD5 (dopamine receptor D5) is highly expressed in the prefrontal cortex, where it regulates cognitive function and memory; its deletion has been linked to impaired neurodevelopment in murine models [18]. Together, haploinsufficiency of WFS1 and DRD5 likely contributes to the patient’s intellectual disability. Our study identifies ovarian dysfunction as a novel phenotypic feature associated with proximal 4p deletions, expanding the clinical spectrum of this chromosomal disorder. This finding contrasts with the report by Tonk et al., who described familial interstitial deletions of 4p15.2p16.1 without observing reproductive impairment in affected individuals [19]. We hypothesize that this phenotypic discrepancy may stem from differences in the deleted chromosomal segments: whereas the deletion in the Tonk cohort was limited to 4p15.2p16.1, our case involves a more extensive deletion spanning 4p15.32p16.2, which may encompass additional genes critical for ovarian function. Within the deleted region, four candidate genes (WFS1, CC2D2A, PROM1, and QDPR) warrant detailed discussion regarding their potential roles in ovarian dysfunction. Among the four candidate genes identified (WFS1, CC2D2A, PROM1, QDPR), WFS1 and PROM1 have plausible roles in ovarian function. In addition to its critical role in neurodevelopment, WFS1 is expressed in ovarian granulosa cells, and its mutations are associated with premature ovarian insufficiency (POI) in humans [20,21]. PROM1 (prominin 1) encodes a stem cell marker critical for folliculogenesis; murine models with Prom1 deletion exhibit impaired ovarian follicle maturation [22]. While CC2D2A and QDPR are primarily linked to ciliopathies and neurotransmitter metabolism, respectively [23,24], their potential roles in ovarian biology warrant exploration, as ciliary dysfunction is increasingly recognized as a driver of POI [25]. We also identified a duplicated segment (16p13.13) containing 19 genes listed in OMIM. However, no associated clinical phenotypes have been reported for this region, and the contribution of these duplicated genes to the patient’s phenotype remains uncertain. In summary, this report describes the first Chinese case of proximal 4p deletion syndrome, characterized by a unique phenotypic profile of ovarian dysfunction, and mild intellectual disability. Our findings expand the clinical and genetic spectrum of the disorder and implicate WFS1, DRD5, CC2D2A, PROM1, and QDPR as candidate genes. These insights may improve clinical recognition of proximal 4p deletion syndrome, particularly in understudied populations, and advance efforts to identify its molecular basis. Declarations Acknowledgments We gratefully acknowledge the support of the proband and her husband. Ethics Statement Research was conducted ethically in accordance with the World Medical Association Declaration of Helsinki. Written informed consent was obtained from the patient for publication of this case report. This study was reviewed and approved by the ethics committee of The First Affiliated Hospital of Guangxi Medical University. Conflict of Interest Statement The authors declare that they have no conflicts of interest. Funding Sources There is no any funding projects that supported this study. Author Contributions Conceived and designed the experiments: Liqiang Wei, Denghe Liu. Performed the experiments: Liqiang Wei. Analyzed the data: Yu He. Contributed reagents/materials/analysis tools: Yu He. Wrote the manuscript: Xiaojv Chi, Xi Qin, Liqiang Wei. Data Availability Statement The data that support the findings of this study are available on request from the corresponding author. CONSENT Written informed consent was obtained from the patient to publish this report in accordance with the journal's patient consent policy. References Lamônica, D., Rosa, K. G., Ribeiro, E., da Rocha, E., Martins, M. F., & Giacheti, C. M. (2025). Clinical features, behaviour and language in Wolf-Hirschhorn syndrome. BMJ case reports, 18(5), e264591. https://doi.org/10.1136/bcr-2024-264591 Bel-Fenellós, C., Biencinto-López, C., Orio-Aparicio, C., da Silva-Mori, X., Tenorio-Castaño, J. A., Lapunzina, P., & Nevado, J. (2025). Family well-being in families with children and young people with Wolf-Hirschhorn Syndrome. 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Supplementary Files table1.xlsx Supplementarytable1.xlsx Cite Share Download PDF Status: Published Journal Publication published 03 Nov, 2025 Read the published version in Molecular Cytogenetics → Version 1 posted Editorial decision: Revision requested 26 Aug, 2025 Reviews received at journal 15 Aug, 2025 Reviews received at journal 14 Aug, 2025 Reviewers agreed at journal 09 Aug, 2025 Reviews received at journal 08 Aug, 2025 Reviewers agreed at journal 05 Aug, 2025 Reviewers agreed at journal 04 Aug, 2025 Reviewers agreed at journal 04 Aug, 2025 Reviews received at journal 04 Aug, 2025 Reviewers agreed at journal 04 Aug, 2025 Reviewers agreed at journal 03 Aug, 2025 Reviewers invited by journal 03 Aug, 2025 Editor assigned by journal 21 Jul, 2025 Submission checks completed at journal 21 Jul, 2025 First submitted to journal 19 Jul, 2025 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. 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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-7165207","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":496191835,"identity":"8804f038-c62e-4e8d-9efd-45bceca120d1","order_by":0,"name":"Liqiang Wei","email":"","orcid":"","institution":"the First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Liqiang","middleName":"","lastName":"Wei","suffix":""},{"id":496191836,"identity":"2d9b0d7a-fa2c-41ef-b4ac-0c90dd92aea8","order_by":1,"name":"Yu He","email":"","orcid":"","institution":"the First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"He","suffix":""},{"id":496191837,"identity":"69775e61-7d3d-44b4-86fc-455a8f64066e","order_by":2,"name":"Denghe Liu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7klEQVRIiWNgGAWjYBACPmYGBgkgncDA3thw4EOFhBw/IS1scC08hw8+nHHGwliygZAWBpgWibRkY862isQNBLWw8xje+LijNo+fIcdMmnGeBOMGBuaHj27gdRiPseXMM8eLJRvOmEkXbpNgNmdgMzbOwa/FTJq37VjihoM9ZtIzt0mwWTbwsEkT1PIXqGX/YZDeORI8BgeI0cLYVpO4gY0t2Zi3QUKCCC1sxZa9bQcSZ5xhBgbyMQkDyWYCfuHnP7zxxs+2usT++Q+BUVlTV9/P3vzwMT4tUHAYic1MWDkI1BGnbBSMglEwCkYmAACcmUklvnn4pwAAAABJRU5ErkJggg==","orcid":"","institution":"the First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":true,"prefix":"","firstName":"Denghe","middleName":"","lastName":"Liu","suffix":""},{"id":496191838,"identity":"c64bd5a1-f5ee-4aec-abd1-0775916ef043","order_by":3,"name":"Xiaojv Chi","email":"","orcid":"","institution":"the First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xiaojv","middleName":"","lastName":"Chi","suffix":""},{"id":496191839,"identity":"a0db8ecc-47ef-40f2-9429-3547c15b8e2c","order_by":4,"name":"Xi Qin","email":"","orcid":"","institution":"Baise Maternal And Child Hospita","correspondingAuthor":false,"prefix":"","firstName":"Xi","middleName":"","lastName":"Qin","suffix":""}],"badges":[],"createdAt":"2025-07-19 14:53:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7165207/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7165207/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13039-025-00735-2","type":"published","date":"2025-11-03T15:57:11+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":88489293,"identity":"3c1f4526-85dd-439a-a15a-008b03fef70a","added_by":"auto","created_at":"2025-08-07 04:03:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":218636,"visible":true,"origin":"","legend":"\u003cp\u003eAn interstitial deletion in 4p was revealed by conventional G-banding chromosome analysis.\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7165207/v1/55d89a08a66d7cdeac458803.png"},{"id":88489292,"identity":"c5d2540d-f223-4389-a88b-1a189ec6f66b","added_by":"auto","created_at":"2025-08-07 04:03:57","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":435516,"visible":true,"origin":"","legend":"\u003cp\u003eNGS-CNVA results showing one copy of deletion on 4p15.32-p16.2 and one copy of duplication on 16p13.13.\u003c/p\u003e","description":"","filename":"figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7165207/v1/e966dfbbeee99d6d7bd91977.png"},{"id":88489295,"identity":"0980b33d-e693-4d3a-928e-f54f5989ca9e","added_by":"auto","created_at":"2025-08-07 04:03:58","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":488585,"visible":true,"origin":"","legend":"\u003cp\u003eVenn diagrams showing the overlap between related genes from databases and deleted genes in the present case. (A) neurodevelopment-related genes from GeneCards and OMIM databases with duplicate entries removed were overlapped with the deleted genes identified in our case. (B) ovarian dysfunction-related genes from GeneCards and OMIM databases after excluding duplicateswere overlapped with the deleted genes detected in our case\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-7165207/v1/252b178b5afc8c4347d65544.png"},{"id":95564830,"identity":"811723e5-4faf-4511-8225-25e765f0d0c3","added_by":"auto","created_at":"2025-11-10 16:10:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1221094,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7165207/v1/234bed44-ac06-4052-9474-def86f1f4f16.pdf"},{"id":88489296,"identity":"bb02502a-6ff0-4345-8f06-c404be15342c","added_by":"auto","created_at":"2025-08-07 04:03:58","extension":"xlsx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":193452,"visible":true,"origin":"","legend":"","description":"","filename":"table1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7165207/v1/79e92e93694d311c5d26558d.xlsx"},{"id":88490441,"identity":"4c535e20-26b5-4da7-9645-55c3cd46dd2c","added_by":"auto","created_at":"2025-08-07 04:11:58","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":14762,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarytable1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7165207/v1/ba840c8c44b7f9c2012a171c.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Proximal 4p Deletion Syndrome in a Woman With Developmental Delay: A Case Report and Literature Review","fulltext":[{"header":"Introduction","content":"\u003cp\u003eChromosomal deletions involving the short arm of chromosome 4 (4p) have been associated with two distinct clinical phenotypes: Wolf-Hirschhorn syndrome (WHS) and proximal 4p deletion syndrome. WHS, primarily caused by distal deletions in the 4p16.3-pter region, is characterized by distinctive craniofacial dysmorphology (e.g., trigonocephaly, broad nasal bridge, and hypoplastic nasal alae), severe developmental delay, and intellectual disability [1,2]. In contrast, proximal 4p deletion syndrome, defined by deletions in the 4p14-p16.1 region, presents with milder clinical manifestations, including mild to moderate intellectual disability, subtle dysmorphic features (e.g., long face, up-slanting palpebral fissures, epicanthal folds, and large lips), and skeletal abnormalities (e.g., pectus excavatum, genuvalga, and joint hyperlaxity) [3,4].\u003c/p\u003e\u003cp\u003eDespite increasing reports of proximal 4p deletions, the syndrome remains understudied, with approximately 37 cases documented in the literature [5]. Most prior studies relied on conventional karyotyping, limiting the precision of deletion mapping; only a subset of cases have been characterized using high-resolution genomic techniques [6\u0026ndash;9]. The molecular basis of proximal 4p deletion syndrome remains unclear, as causative genes have not been definitively identified. Notably, phenotypic variability among reported cases further complicates research. While some patients exhibit classic features like developmental delay and dysmorphology, others present with atypical manifestations [10,11].\u003c/p\u003e\u003cp\u003eHere, we described the first Chinese case of proximal 4p deletion syndrome, characterized by an 11.7 Mb deletion in 4p15.32-p16.2 and a 1.25 Mb microduplication in 16p13.13. The patient presented with ovarian dysfunction, and mild intellectual disability, lacking typical craniofacial features of proximal 4p deletion syndrome. Through genomic database analysis (Genecards and OMIM), we identified candidate genes (e.g., WFS1, DRD5, CC2D2A, PROM1and QDPR) that may contribute to her phenotypes. Furthermore, a systematic review of 38 published cases revealed 20 with overlapping deletion regions, enabling comparative analysis of genotype-phenotype associations. This report aims to: (1) expand the clinical and genetic spectrum of proximal 4p deletion syndrome, (2)provide new insights into potential causative genes, advancing our understanding of this rare syndrome. We hope this report will help make this syndrome more recognizable among clinicians and provide a foundation for identifying the primary causative gene.\u003c/p\u003e\u003cp\u003e\u003cb\u003ePatient presentation\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe proband was a 21-year-old female, who presented to our outpatient service due to primary infertility and ovarian dysfunction. The patient had a history of mental retardation, diagnosed as \"Intellectual Disability Level 3.\" She was able to perform basic activities of daily living, including walking, personal hygiene, and feeding herself. Her medical history revealed that she attained menarche at the age of 13 and had regular menstrual cycles.\u003c/p\u003e\u003cp\u003eOn physical examination, the patient exhibited normal vital signs and systemic functions. Her external genitalia appeared normal, and she had a normal-sized cervix. Transthoracic echocardiography revealed no abnormalities. Laboratory investigations, including routine blood parameters, liver and kidney function tests, myocardial enzymes, blood coagulation profile, thyroid hormones (TH), Human Growth Hormone, ACTH, and sex hormones, were within normal limits. There was no history of seizures according to her parents. The patient presented with a tall and thin body habitus but lacked minor dysmorphic features associated with proximal 4p deletion syndrome. The patient did not undergo specific therapeutic interventions related to her chromosomal abnormality. However, she was counseled regarding the potential implications of her condition on fertility and reproductive health. The proband also had a sister and a brother, who were healthy, but their karyotypes were unavailable. The patient's parents were healthy and did not undergo routine chromosomal analysis.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eRoutine chromosomal analysis using standard G banding revealed a deletion of the short arm of chromosome 4, designated as 46, XX, del(4)(p15.3-p16) (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Subsequent NGS-CNVA testing on the patient\u0026apos;s genomic DNA showed an approximately 11.7 Mb deletion in the 4p15.32-p16.2 region (chr4:g.5776037_17548280del) and an approximately 1.25 Mb duplication in the 16p13.13 region (chr16:g.11263062_12513616dup) (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). A total of 101 genes were deleted in the affected region. Additionally, 19 genes were identified in the duplicated region.\u003c/p\u003e\n\u003cp\u003eA total of 498 genes related to neurodevelopment and 2206 genes related to ovarian dysfunction were collected from the GeneCards and OMIM databases after combining and deleting repetitive genes. The intersection between the genes related to neurodevelopment and ovarian dysfunction and the deleted genes in our case was then identified, serving as potential genes for causal genes. Ultimately, 2 overlapping genes, including WFS1 and DRD5, for the neurodevelopment(Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eA) and 4 ovarian dysfunction-related genes(Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eB), including WFS1, CC2D2A, PROM1 and QDPR, were identified. A review of the literature revealed 37 (Supplementary tabl\u003cspan class=\"InternalRef\"\u003ee1\u003c/span\u003e)reported cases of proximal 4p deletion syndrome, with 19 cases(Table 1) exhibiting an overlap with the deleted region in our patient\u0026apos;s case.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cb\u003eCytogenetic analysis\u003c/b\u003e\u003c/p\u003e\u003cp\u003ePeripheral blood was cultured and harvested using standard cytogenetic protocols. Chromosomal preparations were made using the G-banding technique, which has a resolution between 300 and 400 bands. Twenty metaphase cells were analyzed to determine the chromosomal karyotypes, following the guidelines of the International System of Human Cytogenetic Nomenclature (ISCN2016).\u003c/p\u003e\u003cp\u003e\u003cb\u003eNGS-CNV analysis\u003c/b\u003e\u003c/p\u003e\u003cp\u003eIn addition, NGS-CNV was performed on the proband's genomic DNA, which was extracted from PBMCs. This analysis was carried out using the NovaSeq 6000 platform from Illumina, based in San Diego, CA, United States.\u003c/p\u003e\u003cp\u003e\u003cb\u003eAcquisition of Related Genes\u003c/b\u003e\u003c/p\u003e\u003cp\u003eNeurodevelopment-related genes and ovarian dysfunction related genes were downloaded from databases such as Genecards and OMIM. A Venn diagram was generated using the R 4.4.2 software with R package(ggvenn).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis study describes a first Chinese patient with an 11.7 Mb deletion in 4p15.32-p16.2 and a 1.25 Mb duplication in 16p13.13, presenting with ovarian dysfunction, mild intellectual disability and tall and thin habitus. Classical proximal 4p deletion syndrome, typically caused by deletions involving the 4p16.1-p14 region, is characterized by mild-to-moderate intellectual disability, subtle craniofacial dysmorphisms (e.g., long face, up-slanting palpebral fissures), and skeletal abnormalities (e.g., pectus excavatum, joint hyperlaxity) [12\u0026ndash;13]. Notably, the critical region underlying these classic phenotypes has been suggested to 4p15.2\u0026ndash;15.33: a literature review of 19 cases demonstrated that larger deletions extending into 4p15.2\u0026ndash;15.33 more frequently result in craniofacial dysmorphisms and skeletal abnormalities, presumably due to the disruption of a broader repertoire of genes [14\u0026ndash;16].\u003c/p\u003e\u003cp\u003eIn contrast, our patient presented with only moderate intellectual disability without the aforementioned classic features; instead, she exhibited ovarian dysfunction, a manifestation not previously linked to proximal 4p deletions. This phenotypic discrepancy is attributable to the unique deletion interval in our case: a relatively small (11.7 Mb) deletion restricted to 4p15.32-p16.2, which spares most of the 4p15.2\u0026ndash;15.33 critical region. Preservation of this critical region likely retained key genes governing craniofacial and skeletal development, thereby avoiding dysmorphic features. Importantly, the deleted interval still encompasses genes associated with cognitive function, which likely underpin the observed moderate intellectual disability.​Collectively, these observations highlight that the phenotypic spectrum of proximal 4p deletion syndrome is shaped by both the size of the deletion and the specificity of the involved interval\u0026mdash;with disruption of the 4p15.2\u0026ndash;15.33 critical region being central to the manifestation of classic craniofacial and skeletal abnormalities.\u003c/p\u003e\u003cp\u003eThrough integration of database analysis (GeneCards, OMIM), we identified several candidate genes within the 4p deletion interval that may drive the observed phenotypes. The patient\u0026rsquo;s mild intellectual disability (Level 3) aligns with the syndrome\u0026rsquo;s core feature. Among the deleted genes, WFS1 and DRD5 are strong candidates. WFS1 (Wolfram syndrome 1) encodes a transmembrane protein critical for neurodevelopment and endoplasmic reticulum homeostasis; loss-of-function mutations cause Wolfram syndrome, characterized by intellectual disability and neurodegeneration [17]. DRD5 (dopamine receptor D5) is highly expressed in the prefrontal cortex, where it regulates cognitive function and memory; its deletion has been linked to impaired neurodevelopment in murine models [18]. Together, haploinsufficiency of WFS1 and DRD5 likely contributes to the patient\u0026rsquo;s intellectual disability.\u003c/p\u003e\u003cp\u003eOur study identifies ovarian dysfunction as a novel phenotypic feature associated with proximal 4p deletions, expanding the clinical spectrum of this chromosomal disorder. This finding contrasts with the report by Tonk et al., who described familial interstitial deletions of 4p15.2p16.1 without observing reproductive impairment in affected individuals [19]. We hypothesize that this phenotypic discrepancy may stem from differences in the deleted chromosomal segments: whereas the deletion in the Tonk cohort was limited to 4p15.2p16.1, our case involves a more extensive deletion spanning 4p15.32p16.2, which may encompass additional genes critical for ovarian function. Within the deleted region, four candidate genes (WFS1, CC2D2A, PROM1, and QDPR) warrant detailed discussion regarding their potential roles in ovarian dysfunction. Among the four candidate genes identified (WFS1, CC2D2A, PROM1, QDPR), WFS1 and PROM1 have plausible roles in ovarian function. In addition to its critical role in neurodevelopment, WFS1 is expressed in ovarian granulosa cells, and its mutations are associated with premature ovarian insufficiency (POI) in humans [20,21]. PROM1 (prominin 1) encodes a stem cell marker critical for folliculogenesis; murine models with Prom1 deletion exhibit impaired ovarian follicle maturation [22]. While CC2D2A and QDPR are primarily linked to ciliopathies and neurotransmitter metabolism, respectively [23,24], their potential roles in ovarian biology warrant exploration, as ciliary dysfunction is increasingly recognized as a driver of POI [25].\u003c/p\u003e\u003cp\u003eWe also identified a duplicated segment (16p13.13) containing 19 genes listed in OMIM. However, no associated clinical phenotypes have been reported for this region, and the contribution of these duplicated genes to the patient\u0026rsquo;s phenotype remains uncertain.\u003c/p\u003e\u003cp\u003eIn summary, this report describes the first Chinese case of proximal 4p deletion syndrome, characterized by a unique phenotypic profile of ovarian dysfunction, and mild intellectual disability. Our findings expand the clinical and genetic spectrum of the disorder and implicate WFS1, DRD5, CC2D2A, PROM1, and QDPR as candidate genes. These insights may improve clinical recognition of proximal 4p deletion syndrome, particularly in understudied populations, and advance efforts to identify its molecular basis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe gratefully acknowledge the support of the proband and her husband.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eResearch was conducted ethically in accordance with the World Medical Association Declaration of Helsinki. Written informed consent was obtained from the patient for publication of this case report. This study was reviewed and approved by the ethics committee of The First Affiliated Hospital of Guangxi Medical University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Sources\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;There is no any funding projects that supported this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceived and designed the experiments: Liqiang Wei, Denghe Liu. Performed the experiments: Liqiang Wei. Analyzed the data: Yu He. Contributed reagents/materials/analysis tools: Yu He. Wrote the manuscript:\u0026nbsp;Xiaojv Chi, Xi Qin, Liqiang Wei.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available on request from the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONSENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient to publish this report in accordance with the journal\u0026apos;s patient consent policy.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLam\u0026ocirc;nica, D., Rosa, K. G., Ribeiro, E., da Rocha, E., Martins, M. F., \u0026amp; Giacheti, C. M. (2025). Clinical features, behaviour and language in Wolf-Hirschhorn syndrome. BMJ case reports, 18(5), e264591. https://doi.org/10.1136/bcr-2024-264591\u003c/li\u003e\n\u003cli\u003eBel-Fenell\u0026oacute;s, C., Biencinto-L\u0026oacute;pez, C., Orio-Aparicio, C., da Silva-Mori, X., Tenorio-Casta\u0026ntilde;o, J. A., Lapunzina, P., \u0026amp; Nevado, J. (2025). Family well-being in families with children and young people with Wolf-Hirschhorn Syndrome. Research in developmental disabilities, 160, 104974. https://doi.org/10.1016/j.ridd.2025.104974\u003c/li\u003e\n\u003cli\u003ePang, Y., Zeng, L., Liang, H., Cheng, C., Shan, L., Wang, J., Jiang, N., Pi, G., Yang, L., Chen, A., Xiong, F., \u0026amp; Zhu, S. (2024). Proximal 4p Deletion Syndrome in an Infant With Multiple Systemic Anomalies. Molecular genetics \u0026amp; genomic medicine, 12(9), e70005. https://doi.org/10.1002/mgg3.70005\u003c/li\u003e\n\u003cli\u003eBailey, N. G., South, S. T., Hummel, M., \u0026amp; Wenger, S. L. (2010). 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Pediatrics \u0026amp; Neonatology, 52(3), 165-168. doi:10.1016/j.pedneo.2011.03.009\u003c/li\u003e\n\u003cli\u003eBasinko, A., Douet-Guilbert, N., Parent, P., Blondin, G., Mingam, M., Monot, F., Morel, F., Le Bris, M. J., \u0026amp; De Braekeleer, M. (2008). Familial interstitial deletion of the short arm of chromosome 4 (p15.33-p16.3) characterized by molecular cytogenetic analysis. American journal of medical genetics. Part A, 146A(7), 899\u0026ndash;903. https://doi.org/10.1002/ajmg.a.32138\u003c/li\u003e\n\u003cli\u003ePiovani, G., Borsani, G., Bertini, V., Kalscheuer, V. M., Viertel, P., Bellotti, D., ..., Barlati, S. (2006). Unexpected identification of two interstitial deletions in a patient with a pericentric inversion of a chromosome 4 and an abnormal phenotype. European Journal of Medical Genetics, 49(3), 215-223. doi:10.1016/j.ejmg.2005.07.004\u003c/li\u003e\n\u003cli\u003eStankiewicz, P., \u0026amp; Beaudet, A. L. (2007). Use of array CGH in the evaluation of dysmorphism, malformation, developmental delay, and idiopathic mental retardation. Expert Review of Molecular Diagnostics, 7(3), 301\u0026ndash;311. https://doi.org/10.1586/14737159.7.3.301\u003c/li\u003e\n\u003cli\u003eBoccuto, L., Giorda, R., Gervasini, C., Giglio, S., \u0026amp; Zollino, M. (2010). Phenotypic variability in 4p deletion syndrome: From Wolf-Hirschhorn to subtle clinical presentations. American Journal of Medical Genetics Part A, 152A(10), 2504\u0026ndash;2512. https://doi.org/10.1002/ajmg.a.33564\u003c/li\u003e\n\u003cli\u003eStevenson, R. E., Schwartz, S., \u0026amp; Spector, E. (2006). Genotype-phenotype correlations in chromosomal deletion syndromes: An emerging role for genetic modifiers. American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 142C(1), 3\u0026ndash;10. https://doi.org/10.1002/ajmg.c.30087\u003c/li\u003e\n\u003cli\u003eLee, E. M., Verma, M., Palaniappan, N., Pope, E. M., Lee, S., Blacher, L., Neerumalla, P., An, W., Campbell, T., Brown, C., Hurst, S., Marshall, B., Hershey, T., Nunes, V., L\u0026oacute;pez de Heredia, M., \u0026amp; Urano, F. (2023). Genotype and clinical characteristics of patients with Wolfram syndrome and WFS1-related disorders. Frontiers in genetics, 14, 1198171. https://doi.org/10.3389/fgene.2023.1198171\u003c/li\u003e\n\u003cli\u003eBrewer, L. M., Patel, J., Andrasik, F., Sable, J. J., Williams, M. T., Vorhees, C. V., \u0026amp; Sable, H. J. K. (2025). Auditory Event-Related Potentials in Two Rat Models of Attention-Deficit Hyperactivity Disorder: Evidence of Automatic Attention Deficits in Spontaneously Hypertensive Rats but Not in Latrophilin-3 Knockout Rats. Genes, 16(6), 672. https://doi.org/10.3390/genes16060672\u003c/li\u003e\n\u003cli\u003eTonk, V. S., Jalal, S. M., Gonzalez, J., Kennedy, A., \u0026amp; Velagaleti, G. V. (2003). Familial interstitial deletion of chromosome 4 (p15.2p16.1). Annales de genetique, 46(4), 453\u0026ndash;458. https://doi.org/10.1016/s0003-3995(03)00029-7\u003c/li\u003e\n\u003cli\u003eNoormets, K., K\u0026otilde;ks, S., Kavak, A., Arend, A., Aunapuu, M., Keldrimaa, A., Vasar, E., \u0026amp; Tillmann, V. (2009). Male mice with deleted Wolframin (Wfs1) gene have reduced fertility. Reproductive biology and endocrinology : RB\u0026amp;E, 7, 82. https://doi.org/10.1186/1477-7827-7-82\u003c/li\u003e\n\u003cli\u003eNie, L., Wang, X., Wang, S., Hong, Z., \u0026amp; Wang, M. (2024). Genetic insights into the complexity of premature ovarian insufficiency. Reproductive biology and endocrinology : RB\u0026amp;E, 22(1), 94. https://doi.org/10.1186/s12958-024-01254-2\u003c/li\u003e\n\u003cli\u003eBarnett, K. R., Schilling, C., Greenfeld, C. R., Tomic, D., \u0026amp; Flaws, J. A. (2006). Ovarian follicle development and transgenic mouse models. Human reproduction update, 12(5), 537\u0026ndash;555. https://doi.org/10.1093/humupd/dml022\u003c/li\u003e\n\u003cli\u003eVeleri, S., Manjunath, S. H., Fariss, R. N., May-Simera, H., Brooks, M., Foskett, T. A., Gao, C., Longo, T. A., Liu, P., Nagashima, K., Rachel, R. A., Li, T., Dong, L., \u0026amp; Swaroop, A. (2014). Ciliopathy-associated gene Cc2d2a promotes assembly of subdistal appendages on the mother centriole during cilia biogenesis. Nature communications, 5, 4207. https://doi.org/10.1038/ncomms5207\u003c/li\u003e\n\u003cli\u003eSiems, S. B., Gargareta, V. I., Schadt, L. C., Daguano Gastaldi, V., Jung, R. B., Piepkorn, L., Casaccia, P., Sun, T., Jahn, O., \u0026amp; Werner, H. B. (2025). Developmental maturation and regional heterogeneity but no sexual dimorphism of the murine CNS myelin proteome. Glia, 73(1), 38\u0026ndash;56. https://doi.org/10.1002/glia.24614\u003c/li\u003e\n\u003cli\u003eHildebrandt, F., Benzing, T., \u0026amp; Katsanis, N. (2011). Ciliopathies. The New England journal of medicine, 364(16), 1533\u0026ndash;1543. https://doi.org/10.1056/NEJMra1010172\u003c/li\u003e\n\u003c/ol\u003e\n"},{"header":"Table","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\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":"molecular-cytogenetics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"mocy","sideBox":"Learn more about [Molecular Cytogenetics](http://molecularcytogenetics.biomedcentral.com/)","snPcode":"13039","submissionUrl":"https://submission.nature.com/new-submission/13039/3","title":"Molecular Cytogenetics","twitterHandle":"@OAgenetics","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"4p15.32-16.2, interstitial deletion, 16p13.13 duplication, mental retardation, ovarian dysfunction","lastPublishedDoi":"10.21203/rs.3.rs-7165207/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7165207/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eDeletions in chromosome 4p can lead to two distinct phenotypes, Wolf-Hirschhorn syndrome (WHS) and proximal 4p deletion syndrome. While WHS, associated with distal deletions, has well-characterized phenotypic features, proximal 4p deletion syndrome, involving the 4p14-p 16.1 region, shows milder manifestations, and its causative gene remains unknown with fewer reported cases. Here we report a Chinese case: a 21-year-old female with a peripheral blood chromosomal karyotype of 46,XX,del(4)(p15.3-p16). NGS-CNVA further revealed an 11.7 Mb deletion in the 4p16.2-p15.32 region and a 1.25 Mb microduplication in 16p13.13. She had ovarian dysfunction, and mild mental retardation without typical proximal 4p deletion phenotypes. Through analysis of Genecards and OMIM databases, we identified two genesneurodevelopmental genes DRD5 and WFS1, and four ovarian dysfunction-related genes WFS1, CC2D2A, PROM1, and QDPR, suggesting their roles in the patient's manifestations. Additionally, a review of 38 published cases of proximal 4p deletion syndrome revealed 21 cases with an overlap in the deleted region with our case. This report not only enhances the recognition of this rare syndrome among clinicians but also provides a basis for further exploration of the potential causative genes, contributing to a better understanding of the genotype-phenotype correlations in proximal 4p deletion syndrome.\u003c/p\u003e","manuscriptTitle":"Proximal 4p Deletion Syndrome in a Woman With Developmental Delay: A Case Report and Literature Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-07 04:03:53","doi":"10.21203/rs.3.rs-7165207/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-08-26T13:57:46+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-15T04:39:48+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-14T11:39:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"317957181281788548092129788854431852890","date":"2025-08-09T10:25:16+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-08T12:38:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"50127368139866323130922030472419601154","date":"2025-08-05T18:59:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"254735683499502394140890072805085510039","date":"2025-08-04T11:09:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"228185307599669193013639510135458854428","date":"2025-08-04T09:09:33+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-04T07:29:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"46203311327460814767147991307296106956","date":"2025-08-04T07:05:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"13844716402535736389100392017667583871","date":"2025-08-03T18:04:19+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-03T18:00:31+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-21T08:10:03+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-21T08:07:17+00:00","index":"","fulltext":""},{"type":"submitted","content":"Molecular Cytogenetics","date":"2025-07-19T14:44:44+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"molecular-cytogenetics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"mocy","sideBox":"Learn more about [Molecular Cytogenetics](http://molecularcytogenetics.biomedcentral.com/)","snPcode":"13039","submissionUrl":"https://submission.nature.com/new-submission/13039/3","title":"Molecular Cytogenetics","twitterHandle":"@OAgenetics","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5f6fcbde-61bf-4af4-b91d-7492137d3162","owner":[],"postedDate":"August 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-10T16:09:39+00:00","versionOfRecord":{"articleIdentity":"rs-7165207","link":"https://doi.org/10.1186/s13039-025-00735-2","journal":{"identity":"molecular-cytogenetics","isVorOnly":false,"title":"Molecular Cytogenetics"},"publishedOn":"2025-11-03 15:57:11","publishedOnDateReadable":"November 3rd, 2025"},"versionCreatedAt":"2025-08-07 04:03:53","video":"","vorDoi":"10.1186/s13039-025-00735-2","vorDoiUrl":"https://doi.org/10.1186/s13039-025-00735-2","workflowStages":[]},"version":"v1","identity":"rs-7165207","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7165207","identity":"rs-7165207","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}