Qi Fang, Lanxi Ran, Song Liu, Jianyong Di, Ye Liu, Fengqin Xu, Binbin Wang
{"title":"一种新的MCMDC2变异在一个近亲中国家庭中引起减数分裂停止和非阻塞性无精子症。","authors":"Qi Fang, Lanxi Ran, Song Liu, Jianyong Di, Ye Liu, Fengqin Xu, Binbin Wang","doi":"10.1038/s10038-025-01397-z","DOIUrl":null,"url":null,"abstract":"<p><p>Non-obstructive azoospermia (NOA) is often associated with genetic variants. Whole-exome sequencing (WES) has emerged as a powerful tool in studying the genetic diagnosis of NOA and to help identify novel causal gene variants. Minichromosome maintenance domain-containing 2 (MCMDC2), an atypical yet conserved MCM protein, plays a key role in meiotic recombination and the maintenance of fertility. To date, only a limited number of MCMDC2 variants have been reported. The current study identified a novel deleterious variant (c.G226T/p.Val76Phe) of MCMDC2 by WES in a patient with NOA from a consanguineous Chinese family. Bioinformatics analysis indicated that the altered amino acid is highly conserved, and the c.G226T/p.Val76Phe variant may affect the structure and function of the MCMDC2 protein. Our results provide new insights into the underlying etiology of NOA in humans, further expanding the mutant spectrum of MCMDC2.</p>","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":2.5000,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A novel MCMDC2 variant causes meiotic arrest and non-obstructive azoospermia in a consanguineous Chinese family.\",\"authors\":\"Qi Fang, Lanxi Ran, Song Liu, Jianyong Di, Ye Liu, Fengqin Xu, Binbin Wang\",\"doi\":\"10.1038/s10038-025-01397-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Non-obstructive azoospermia (NOA) is often associated with genetic variants. Whole-exome sequencing (WES) has emerged as a powerful tool in studying the genetic diagnosis of NOA and to help identify novel causal gene variants. Minichromosome maintenance domain-containing 2 (MCMDC2), an atypical yet conserved MCM protein, plays a key role in meiotic recombination and the maintenance of fertility. To date, only a limited number of MCMDC2 variants have been reported. The current study identified a novel deleterious variant (c.G226T/p.Val76Phe) of MCMDC2 by WES in a patient with NOA from a consanguineous Chinese family. Bioinformatics analysis indicated that the altered amino acid is highly conserved, and the c.G226T/p.Val76Phe variant may affect the structure and function of the MCMDC2 protein. Our results provide new insights into the underlying etiology of NOA in humans, further expanding the mutant spectrum of MCMDC2.</p>\",\"PeriodicalId\":16077,\"journal\":{\"name\":\"Journal of Human Genetics\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2025-09-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Human Genetics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1038/s10038-025-01397-z\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Human Genetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s10038-025-01397-z","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
A novel MCMDC2 variant causes meiotic arrest and non-obstructive azoospermia in a consanguineous Chinese family.
Non-obstructive azoospermia (NOA) is often associated with genetic variants. Whole-exome sequencing (WES) has emerged as a powerful tool in studying the genetic diagnosis of NOA and to help identify novel causal gene variants. Minichromosome maintenance domain-containing 2 (MCMDC2), an atypical yet conserved MCM protein, plays a key role in meiotic recombination and the maintenance of fertility. To date, only a limited number of MCMDC2 variants have been reported. The current study identified a novel deleterious variant (c.G226T/p.Val76Phe) of MCMDC2 by WES in a patient with NOA from a consanguineous Chinese family. Bioinformatics analysis indicated that the altered amino acid is highly conserved, and the c.G226T/p.Val76Phe variant may affect the structure and function of the MCMDC2 protein. Our results provide new insights into the underlying etiology of NOA in humans, further expanding the mutant spectrum of MCMDC2.
期刊介绍:
The Journal of Human Genetics is an international journal publishing articles on human genetics, including medical genetics and human genome analysis. It covers all aspects of human genetics, including molecular genetics, clinical genetics, behavioral genetics, immunogenetics, pharmacogenomics, population genetics, functional genomics, epigenetics, genetic counseling and gene therapy.
Articles on the following areas are especially welcome: genetic factors of monogenic and complex disorders, genome-wide association studies, genetic epidemiology, cancer genetics, personal genomics, genotype-phenotype relationships and genome diversity.