NR5A1 (SF-1) gene variants in a group of 26 young women with XX primary ovarian insufficiency

Objective: To determine whether NR5A1 (SF-1) variants are a cause of primary ovarian insufficiency (POI) in 26 young women with similar genetic background. Design: Genetic and functional mutation study. Setting: University hospitals. Patient(s): Genetic analysis of the NR5A1 gene in 26 XX girls with POI. Intervention(s): None. Main Outcome Measure(s): NR5A1 molecular and functional analysis. Result(s): Genetic analysis revealed a new c.763C>T (p.Arg255Cys) mutation and a recurrent c.437G>C (p.Gly146Ala) variant. Functional analysis of the p.Arg255Cys mutant showed a marked decrease in transactivation on the Cyp11a1 and Amh promoters. The p.Gly146Ala variant was identified significantly more often in the patients (46.1%) than in ancestry-matched control subjects (10%). Conclusion(s): We identified one new NR5A1 mutation in a patient of our POI cohort (prevalence 3.8%). Moreover, although our study is limited in the number of cases, we report the high frequency of the p.Gly146Ala variant in this cohort compared with the ancestry-matched control subjects. This work highlights the important role of SF-1 in ovarian function.