A Biallelic Mutation in the Homologous Recombination Repair Gene SPIDR Is Associated With Human Gonadal Dysgenesis

Context:Primary ovarian insufficiency (POI) is caused by ovarian follicle depletion or follicle dysfunction, characterized by amenorrhea with elevated gonadotropin levels. The disorder presents as absence of normal progression of puberty.Objective:To elucidate the cause of ovarian dysfunction in a family with POI.Design:We performed whole exome sequencing in two affected individuals. To evaluate whether DNA double-stranded break (DSB) repair activities are altered in biallelic mutation carriers we applied an EGFP-based assay for the detection of specific DSB repair pathways in blood-derived cells.Setting:Diagnoses were made at the Pediatric Endocrine Clinic, Clalit Health Services, Israel. Genetic counseling and sample collection were performed at the Pediatric Genetics Unit, Schneider Children's Medical Center Israel, Petah Tikva, Israel.Patients:Two sisters born to consanguineous parents of Israeli Muslim Arab ancestry presented with a lack of normal progression of puberty, high gonadotropin levels and ...