{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["29(12)"],"submitter":["Franca MM"],"pubmed_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<sup>c.92delT/c.92delT</sup> 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"],"journal":["Cell death and differentiation"],"pagination":["2347-2361"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9751091"],"repository":["biostudies-literature"],"pubmed_title":["A truncating variant of RAD51B associated with primary ovarian insufficiency provides insights into its meiotic and somatic functions."],"pmcid":["PMC9751091"],"pubmed_authors":["Astudillo A","Franca MM","Sanchez-Saez F","Llano E","Condezo YB","Munoz S","Sanchez-Martin MA","Martin-Hervas MR","Sainz-Urruela R","Veitia RA","Felipe-Medina N","Mendez J","Pendas AM","Mendonca BB","Elzaiat M","Garcia-Valiente R"],"additional_accession":[]},"is_claimable":false,"name":"A truncating variant of RAD51B associated with primary ovarian insufficiency provides insights into its meiotic and somatic functions.","description":"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<sup>c.92delT/c.92delT</sup> 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","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2025-04-22T13:16:57.451Z","creation":"2025-04-06T00:35:46.247Z"},"accession":"S-EPMC9751091","cross_references":{"pubmed":["35624308"],"doi":["10.1038/s41418-022-01021-z"]}}