Polina N Tsabai, Nadezhda S Pavlova, Taras V Shatylko, Zaira Kh Kumykova, Olga K Stupko, Taisya O Kochetkova, Nataliia N Lobanova, Andrey Yu Goltsov, Olga O Leukhina, Jekaterina Shubina, Safar I Gamidov, Elena V Uvarova, Dmitry Yu Trofimov
{"title":"Novel STAG3 variant causes oligoasthenoteratozoospermia with high sperm aneuploidy rate.","authors":"Polina N Tsabai, Nadezhda S Pavlova, Taras V Shatylko, Zaira Kh Kumykova, Olga K Stupko, Taisya O Kochetkova, Nataliia N Lobanova, Andrey Yu Goltsov, Olga O Leukhina, Jekaterina Shubina, Safar I Gamidov, Elena V Uvarova, Dmitry Yu Trofimov","doi":"10.1007/s10815-025-03417-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Premature ovarian insufficiency (POI) and non-obstructive azoospermia (NOA) are the most severe forms of infertility. Pathogenic variants in a number of genes cause both disorders in siblings. One of them is STAG3, which encodes a meiosis-specific subunit of a cohesin complex. Here, we searched for genetic cause of oligoasthenoteratozoospermia (OAT) and POI within one family.</p><p><strong>Methods: </strong>The proband was a 16-year-old girl with secondary amenorrhea. She was diagnosed with hypergonadotropic hypogonadism and streak ovaries. She had normal karyotype 46,XX and no premutation in FMR1 gene. Her 28-year-old brother was diagnosed with severe oligoasthenoteratozoospermia (OAT) syndrome. The aneuploidy rate in his sperm was assessed by FISH assay and appeared to be extremely high with only 5% of morphologically normal spermatozoa being haploid. He had normal karyotype 46,XY and no AZF microdeletions.</p><p><strong>Results: </strong>Whole exome sequencing identified two likely pathogenic heterozygous truncating variants in STAG3 gene, prevously described p.Arg926Ter and novel p.Glu1184Ter. Sanger sequencing showed that both the patient and her brother were compound heterozygotes.</p><p><strong>Conclusion: </strong>In this study, we suggest the association of the identified variants in STAG3 gene with OAT syndrome and POI and describe the third familial case of STAG3-related infertility.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":"1239-1245"},"PeriodicalIF":2.7000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055683/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Assisted Reproduction and Genetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10815-025-03417-5","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/11 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose: Premature ovarian insufficiency (POI) and non-obstructive azoospermia (NOA) are the most severe forms of infertility. Pathogenic variants in a number of genes cause both disorders in siblings. One of them is STAG3, which encodes a meiosis-specific subunit of a cohesin complex. Here, we searched for genetic cause of oligoasthenoteratozoospermia (OAT) and POI within one family.
Methods: The proband was a 16-year-old girl with secondary amenorrhea. She was diagnosed with hypergonadotropic hypogonadism and streak ovaries. She had normal karyotype 46,XX and no premutation in FMR1 gene. Her 28-year-old brother was diagnosed with severe oligoasthenoteratozoospermia (OAT) syndrome. The aneuploidy rate in his sperm was assessed by FISH assay and appeared to be extremely high with only 5% of morphologically normal spermatozoa being haploid. He had normal karyotype 46,XY and no AZF microdeletions.
Results: Whole exome sequencing identified two likely pathogenic heterozygous truncating variants in STAG3 gene, prevously described p.Arg926Ter and novel p.Glu1184Ter. Sanger sequencing showed that both the patient and her brother were compound heterozygotes.
Conclusion: In this study, we suggest the association of the identified variants in STAG3 gene with OAT syndrome and POI and describe the third familial case of STAG3-related infertility.
期刊介绍：
The Journal of Assisted Reproduction and Genetics publishes cellular, molecular, genetic, and epigenetic discoveries advancing our understanding of the biology and underlying mechanisms from gametogenesis to offspring health. Special emphasis is placed on the practice and evolution of assisted reproduction technologies (ARTs) with reference to the diagnosis and management of diseases affecting fertility. Our goal is to educate our readership in the translation of basic and clinical discoveries made from human or relevant animal models to the safe and efficacious practice of human ARTs. The scientific rigor and ethical standards embraced by the JARG editorial team ensures a broad international base of expertise guiding the marriage of contemporary clinical research paradigms with basic science discovery. JARG publishes original papers, minireviews, case reports, and opinion pieces often combined into special topic issues that will educate clinicians and scientists with interests in the mechanisms of human development that bear on the treatment of infertility and emerging innovations in human ARTs. The guiding principles of male and female reproductive health impacting pre- and post-conceptional viability and developmental potential are emphasized within the purview of human reproductive health in current and future generations of our species.
The journal is published in cooperation with the American Society for Reproductive Medicine, an organization of more than 8,000 physicians, researchers, nurses, technicians and other professionals dedicated to advancing knowledge and expertise in reproductive biology.
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