biostudies-literatureUnknown29(12)Franca MMPrimary 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 HELQCell death and differentiation2347-2361https://www.ebi.ac.uk/biostudies/studies/S-EPMC9751091biostudies-literatureA truncating variant of RAD51B associated with primary ovarian insufficiency provides insights into its meiotic and somatic functions.PMC9751091Astudillo AFranca MMSanchez-Saez FLlano ECondezo YBMunoz SSanchez-Martin MAMartin-Hervas MRSainz-Urruela RVeitia RAFelipe-Medina NMendez JPendas AMMendonca BBElzaiat MGarcia-Valiente RfalseA truncating variant of RAD51B associated with primary ovarian insufficiency provides insights into its meiotic and somatic functions.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 HELQ2022-01-01T00:00:00Z2022 Dec2025-04-22T13:16:57.451Z2025-04-06T00:35:46.247ZS-EPMC97510913562430810.1038/s41418-022-01021-z