A truncating variant of RAD51B associated with primary ovarian insufficiency provides insights into its meiotic and somatic functions.

ABSTRACT: Primary ovarian insufficiency (POI) causes female infertility by abolishing normal ovarian function. Although its genetic etiology has been extensively investigated, most POI cases remain unexplained. Using whole-exome sequencing, we identified a homozygous variant in RAD51B -(c.92delT) in two sisters with POI. In vitro studies revealed that this variant leads to translation reinitiation at methionine 64. Here, we show that this is a pathogenic hypomorphic variant in a mouse model. Rad51b^{c.92delT/c.92delT} mice exhibited meiotic DNA repair defects due to RAD51 and HSF2BP/BMRE1 accumulation in the chromosome axes leading to a reduction in the number of crossovers. Interestingly, the interaction of RAD51B-c.92delT with RAD51C and with its newly identified interactors RAD51 and HELQ

SUBMITTER: Franca MM 

PROVIDER: S-EPMC9751091 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature