Variants in Homologous Recombination Genes EXO1 and RAD51 Related with Premature Ovarian Insufficiency.

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. To investigate the role of variations in homologous recombination genes played in POI pathogenesis. 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. 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. Our study first linked the variants of EXO1 and RAD51 with POI and further highlighted the role of DNA repair genes in ovarian dysgenesis. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Citation

Wei Luo, Ting Guo, Guangyu Li, Ran Liu, Shidou Zhao, Meihui Song, Liangran Zhang, Shunxin Wang, Zi-Jiang Chen, Yingying Qin. Variants in Homologous Recombination Genes EXO1 and RAD51 Related with Premature Ovarian Insufficiency. The Journal of clinical endocrinology and metabolism. 2020 Oct 01;105(10)

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PMID: 32772095

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