Novel Variants in MDC1 Were Associated With Severe Oligoasthenoteratozoospermia.

IF 2.3 3区 医学 Q2 GENETICS & HEREDITY
Xu Liu, Yu Wang, Chen Tan, Hujia Tan, Wenjun Wang, Pengcheng Hu, Yunxia Cao, Fengsong Wang, Yichang Lu, Fuxi Zhu
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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.

MDC1基因的新变异与严重少弱异性精子症相关。
DNA损伤检查点1 (MDC1)是一种与DNA损伤修复密切相关的蛋白质。最近,我们在两例严重少弱异性精子症(OAT)患者中发现了三种新的MDC1变异(NM_014641.3: c.c c5977t; p.R1993X) (NM_014641.3: c.c c5644t; p.R1882X; c.A1T; p.M1L)。体外验证表明,p.R1882X变异导致MDC1蛋白被截断,p.R1993X变异导致MDC1蛋白被截断后降解。免疫荧光显示,由变异引起的截断蛋白影响了MDC1与其相互作用蛋白γH2AX的共定位关系。此外,其中一名患者及其妻子接受了卵胞浆内单精子注射(ICSI),但结果不令人满意。我们首次筛选出OAT患者的MDC1变异,本研究可为患者提供精确的基因诊断。它拓宽了MDC1的变异谱,有利于制定靶向治疗策略。
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来源期刊
Clinical Genetics
Clinical Genetics 医学-遗传学
CiteScore
6.50
自引率
0.00%
发文量
175
审稿时长
3-8 weeks
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
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