CHEK1变异是卵巢功能不全的危险因素，通过代谢和炎症相关基因的错误调节。

IF 3.8 3区医学 Q2 GENETICS & HEREDITY

Human Genomics Pub Date : 2025-06-18 DOI:10.1186/s40246-025-00774-1

Jianying Guo, Yali Fan, Zifan Song, Lin Li, Meng Fu

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引用次数: 0

摘要

背景：卵巢早衰（POI）影响着大约1%的女性，并且越来越多地导致女性不孕。POI的病因是不同的。CHEK1是DNA损伤和复制应激反应的关键组成部分，最近被认为与女性生殖生物学有关。结果：我们鉴定出CHEK1变异c.77C > G；通过全外显子组测序在POI患者中发现p.A26G。蛋白结构预测和致病性分析提示CHEK1 A26G变异可能影响蛋白稳定性。过表达野生型和A26G CHEK1的293FT细胞的RNA测序结果显示，代谢和炎症相关基因的表达改变和剪接选择性。结论：CHEK1可能参与卵巢衰老，A26G变异可能增加POI易感性。

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CHEK1 variant is a risk factor for premature ovarian insufficiency by mis- regulating metabolism and inflammation-related genes.

Background: 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.

Results: 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.

Conclusion: CHEK1 may be involved in ovarian aging and the A26G variant may increase susceptibility to POI.

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来源期刊

Human Genomics GENETICS & HEREDITY-

CiteScore

6.00

自引率

2.20%

发文量

审稿时长

11 weeks

期刊介绍： Human Genomics is a peer-reviewed, open access, online journal that focuses on the application of genomic analysis in all aspects of human health and disease, as well as genomic analysis of drug efficacy and safety, and comparative genomics. Topics covered by the journal include, but are not limited to: pharmacogenomics, genome-wide association studies, genome-wide sequencing, exome sequencing, next-generation deep-sequencing, functional genomics, epigenomics, translational genomics, expression profiling, proteomics, bioinformatics, animal models, statistical genetics, genetic epidemiology, human population genetics and comparative genomics.