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.