期刊
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 105, 期 10, 页码 -出版社
ENDOCRINE SOC
DOI: 10.1210/clinem/dgaa505
关键词
POI; DNA repair; EXO1; RAD51; whole exome sequencing
资金
- National Key Research & Developmental Program of China [2017YFC1001100, 2018YFC1003400]
- National Natural Science Foundation of China [81571406, 81522018, 81771541, 31601198]
- Shandong University Education Foundation Public Welfare Project [23460047102008]
- Science Foundation for Distinguished Young Scholars of Shandong [ZR201702150261]
- Shandong Provincial Natural Science Foundation [JQ201605]
- Key Research and Development Plan of Shandong Province [2018GSF118219]
Context: Premature ovarian insufficiency (POI) is characterized by cessation of menstruation before 40 years of age and elevated serum level of FSH (>25 IU/L). Recent studies have found a few causative genes responsible for POI enriched in meiotic recombination and DNA damage repair pathways. Objective: To investigate the role of variations in homologous recombination genes played in POI pathogenesis. Methods: The whole exome sequencing was performed in 50 POI patients with primary amenorrhea. Functional characterizations of the novel variants were carried out in budding yeast and human cell line. Results: We identified 8 missense variants in 7 homologous recombination genes, including EXO1, RAD51, RMI1, MSH5, MSH2, MSH6, and MLH1. The mutation p.Thr52Ser in EXO1 impaired the meiotic process of budding yeast and p.Glu68Gly in RAD51-altered protein localization in human cells, both of them impaired the efficiency of homologous recombination repair for DNA double-stranded breaks in human cells. Conclusions: Our study first linked the variants of EXO1 and RAD51 with POI and further highlighted the role of DNA repair genes in ovarian dysgenesis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据