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

Capsule:
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.

Authors:
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

Abstract:

Objective:
To determine whether NR5A1 variants are a cause of 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 primary ovarian insufficiency.

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

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