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

ObjectiveTo determine whether NR5A1 (SF-1) variants are a cause of primary ovarian insufficiency (POI) in 26 young women with similar genetic background.DesignGenetic and functional mutation study.SettingUniversity 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.