NR5A1 SF1 gene variants in a group of 26 young women with XX primary ovarian insufficiency

In a primary ovarian insufficiency group, we identified one mutation and a frequent variant of the NR5A1/SF-1 gene. This work confirms the important role of steroidogenic factor 1 in ovarian function.


Pascal Philibert, Pharm.D., Ph.D., Françoise Paris, M.D., Ph.D., Besma Lakha, Ph.D., Françoise Audran, Pharm.D., Laura Gaspari, M.D., Ali Saâd, M.D., Ph.D., Sophie Christin-Maître, M.D., Ph.D., Philippe Bouchard, M.D., Ph.D., Charles Sultan, M.D., Ph.D.

Volume 99, Issue 2, Pages 484-489, February 2013



To determine whether NR5A1 variants are a cause of POI in 26 young women with similar genetic background.


Genetic and functional mutation study.


University hospitals.


Genetic analysis of the NR5A1 gene in 26 XX girls with primary ovarian insufficiency.



Main Outcome Measure(s):

NR5A1 molecular and functional analysis.


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 controls (10%).


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 controls. This work highlights the important role of SF-1 in ovarian function.

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