Guo Jianying, Fan Yali, Song Zifan, Li Lin, Fu Meng
State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.
National Clinical Research Center for Obstetrics and Gynecology, Beijing, 100191, China.
Hum Genomics. 2025 Jun 18;19(1):67. doi: 10.1186/s40246-025-00774-1.
Premature ovarian insufficiency (POI) is affecting approximately 1% of females and increasingly contributing to female infertility. The etiology of POI is heterogeneous. CHEK1, a critical component of the DNA damage and replication stress response, has recently been linked to female reproductive biology.
We identified a CHEK1 variant c.77C > G; p.A26G in a POI patient through whole-exome sequencing. Protein structure prediction and pathogenicity analysis suggested that the CHEK1 A26G variant may affect protein stability. RNA sequencing results of 293FT cells overexpressing wild-type and A26G CHEK1 revealed altered expression and alternative splicing of genes involved in metabolism and inflammation.
CHEK1 may be involved in ovarian aging and the A26G variant may increase susceptibility to POI.
卵巢早衰（POI）影响着约1%的女性，并且在女性不孕中所占比例日益增加。POI的病因具有异质性。CHEK1是DNA损伤和复制应激反应的关键组成部分，最近已与女性生殖生物学联系起来。
我们通过全外显子组测序在一名POI患者中鉴定出CHEK1变异体c.77C＞G；p.A26G。蛋白质结构预测和致病性分析表明，CHEK1 A26G变异体可能影响蛋白质稳定性。对过表达野生型和A26G CHEK1的293FT细胞进行RNA测序的结果显示，参与代谢和炎症的基因表达和可变剪接发生了改变。
CHEK1可能参与卵巢衰老，A26G变异体可能增加患POI的易感性。
