{"title":"Detection and Genetic Analysis of Small Supernumerary Marker Chromosomes in Prenatal Diagnosis.","authors":"Jiangfeng Qin, Yanfei Zeng, Yinghua Luo, Biyu Lu, Jiaolian Ya, Pengfei Cai, Ling Zhang, Yan Mei, Dejian Yuan, Xiaoni Wei, Yuchan Xu","doi":"10.1159/000546051","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Small supernumerary marker chromosomes (sSMCs) are small structurally abnormal chromosomes whose origin and structure are difficult to determine by conventional cytogenetic banding techniques. The aims of the study were to analyze sSMCs discovered in prenatal diagnosis, explore the origin and clinical significance of fetal sSMCs, and inform genetic counseling and reproductive health care.</p><p><strong>Methods: </strong>Karyotyping was performed on pregnant women who underwent prenatal diagnosis in a Chinese hospital between April 2018 and April 2024. The sSMC cases encountered were further analyzed using copy number variation sequencing (CNV-seq) to determine the origin of the sSMCs and assess their clinical significance. Uniparental disomy (UPD) was excluded in the families with de novo sSMC cases using multiplex fluorescence PCR and capillary electrophoresis.</p><p><strong>Results: </strong>Out of 30,114 prenatal samples, 30 cases of sSMCs were identified, yielding a detection rate of 0.10%. Family analysis was performed on 23 of these cases, revealing 4 cases inherited and 19 cases of de novo aberrations. CNV-seq was conducted on 27 cases, with 14 showing no abnormalities and 13 exhibiting CNVs. Among the 10 cases where the origin of the sSMC was clearly identified, the duplications involved chromosomes 4, 10, 12, 15, 18, X, and Y, with pathogenic CNVs accounting for 70.0% (7/10) and variants of uncertain clinical significance accounting for 30.0% (3/10). Out of the 30 women with sSMCs detected, 13 chose to terminate the pregnancy, representing 43.3% (13/30). A follow-up was conducted on 13 de novo sSMC cases that were negative for CNV-seq. Among the live-born fetuses, all except one, who presented with speech delay, showed normal clinical features. UPD testing was successfully performed on 3 families (including the 3-year-old girl with speech delay), and all results were negative.</p><p><strong>Conclusion: </strong>Utilizing both karyotyping and molecular genetic testing is advantageous for effectively screening and identifying sSMCs. CNV-seq is recommended as an important supplementary method for sSMC identification, thereby providing more detailed genetic counseling for prenatal diagnosis.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"1-15"},"PeriodicalIF":1.7000,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cytogenetic and Genome Research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1159/000546051","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Small supernumerary marker chromosomes (sSMCs) are small structurally abnormal chromosomes whose origin and structure are difficult to determine by conventional cytogenetic banding techniques. The aims of the study were to analyze sSMCs discovered in prenatal diagnosis, explore the origin and clinical significance of fetal sSMCs, and inform genetic counseling and reproductive health care.
Methods: Karyotyping was performed on pregnant women who underwent prenatal diagnosis in a Chinese hospital between April 2018 and April 2024. The sSMC cases encountered were further analyzed using copy number variation sequencing (CNV-seq) to determine the origin of the sSMCs and assess their clinical significance. Uniparental disomy (UPD) was excluded in the families with de novo sSMC cases using multiplex fluorescence PCR and capillary electrophoresis.
Results: Out of 30,114 prenatal samples, 30 cases of sSMCs were identified, yielding a detection rate of 0.10%. Family analysis was performed on 23 of these cases, revealing 4 cases inherited and 19 cases of de novo aberrations. CNV-seq was conducted on 27 cases, with 14 showing no abnormalities and 13 exhibiting CNVs. Among the 10 cases where the origin of the sSMC was clearly identified, the duplications involved chromosomes 4, 10, 12, 15, 18, X, and Y, with pathogenic CNVs accounting for 70.0% (7/10) and variants of uncertain clinical significance accounting for 30.0% (3/10). Out of the 30 women with sSMCs detected, 13 chose to terminate the pregnancy, representing 43.3% (13/30). A follow-up was conducted on 13 de novo sSMC cases that were negative for CNV-seq. Among the live-born fetuses, all except one, who presented with speech delay, showed normal clinical features. UPD testing was successfully performed on 3 families (including the 3-year-old girl with speech delay), and all results were negative.
Conclusion: Utilizing both karyotyping and molecular genetic testing is advantageous for effectively screening and identifying sSMCs. CNV-seq is recommended as an important supplementary method for sSMC identification, thereby providing more detailed genetic counseling for prenatal diagnosis.
期刊介绍:
During the last decades, ''Cytogenetic and Genome Research'' has been the leading forum for original reports and reviews in human and animal cytogenetics, including molecular, clinical and comparative cytogenetics. In recent years, most of its papers have centered on genome research, including gene cloning and sequencing, gene mapping, gene regulation and expression, cancer genetics, comparative genetics, gene linkage and related areas. The journal also publishes key papers on chromosome aberrations in somatic, meiotic and malignant cells. Its scope has expanded to include studies on invertebrate and plant cytogenetics and genomics. Also featured are the vast majority of the reports of the International Workshops on Human Chromosome Mapping, the reports of international human and animal chromosome nomenclature committees, and proceedings of the American and European cytogenetic conferences and other events. In addition to regular issues, the journal has been publishing since 2002 a series of topical issues on a broad variety of themes from cytogenetic and genome research.