A homozygous hypomorphic BRCA2 variant causes primary ovarian insufficiency without cancer or Fanconi anemia traits

摘要: ABSTRACT Primary Ovarian insufficiency (POI) affects 1% of women under forty. We studied a patient with non-syndromic POI, from consanguineous Turkish family. Exome sequencing identified homozygous missense variant c.8524C>T/p.R2842C in BRCA2. BRCA2 is major player homologous recombination (HR). deficiency induces cancer predisposition and Fanconi Anemia (FA). Remarkably, neither the nor her family exhibit somatic pathologies. The patient’s cells presented intermediate levels chromosomal breaks, cell proliferation radiation-induced RAD51 foci formation when compared to controls, heterozygous mother’s FA cells. R2842C-BRCA2 partially complemented depletion for double-strand break-induced HR. residual HR function could explain absence pathology. expressed human fetal ovaries pachytene stage oocytes, meiotic occurs. This study has impact on understanding genome maintenance management POI patients.