{"title":"Novel Variants in MDC1 Were Associated With Severe Oligoasthenoteratozoospermia.","authors":"Xu Liu, Yu Wang, Chen Tan, Hujia Tan, Wenjun Wang, Pengcheng Hu, Yunxia Cao, Fengsong Wang, Yichang Lu, Fuxi Zhu","doi":"10.1111/cge.70058","DOIUrl":null,"url":null,"abstract":"<p><p>Mediator of DNA damage checkpoint 1 (MDC1) is a protein closely associated with the repair of DNA damage. Recently, we identified three novel variants (NM_014641.3:c.C5977T; p.R1993X) (NM_014641.3:c.C5644T; p.R1882X; c.A1T; p.M1L) in MDC1 in two patients with severe oligoasthenoteratozoospermia (OAT). In vitro validation showed that the p.R1882X variant resulted in the truncation of the MDC1 protein, and the p.R1993X variant resulted in the degradation of the MDC1 protein after truncation. Immunofluorescence demonstrated that the truncated protein caused by the variants affected the colocalization relationship between MDC1 and its interacting protein γH2AX. Additionally, one of the patients and his wife underwent intracytoplasmic sperm injection (ICSI), but the result was unsatisfactory. We screened out the variants of MDC1 in patients with OAT for the first time, and this research could afford precise genetic diagnosis for the patients. It has broadened the variant spectrum of MDC1, which is conducive to the development of targeted therapeutic strategies.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Genetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/cge.70058","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
Mediator of DNA damage checkpoint 1 (MDC1) is a protein closely associated with the repair of DNA damage. Recently, we identified three novel variants (NM_014641.3:c.C5977T; p.R1993X) (NM_014641.3:c.C5644T; p.R1882X; c.A1T; p.M1L) in MDC1 in two patients with severe oligoasthenoteratozoospermia (OAT). In vitro validation showed that the p.R1882X variant resulted in the truncation of the MDC1 protein, and the p.R1993X variant resulted in the degradation of the MDC1 protein after truncation. Immunofluorescence demonstrated that the truncated protein caused by the variants affected the colocalization relationship between MDC1 and its interacting protein γH2AX. Additionally, one of the patients and his wife underwent intracytoplasmic sperm injection (ICSI), but the result was unsatisfactory. We screened out the variants of MDC1 in patients with OAT for the first time, and this research could afford precise genetic diagnosis for the patients. It has broadened the variant spectrum of MDC1, which is conducive to the development of targeted therapeutic strategies.
期刊介绍:
Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice.
Topics of particular interest are:
• Linking genetic variations to disease
• Genome rearrangements and disease
• Epigenetics and disease
• The translation of genotype to phenotype
• Genetics of complex disease
• Management/intervention of genetic diseases
• Novel therapies for genetic diseases
• Developmental biology, as it relates to clinical genetics
• Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease