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

Fertil Steril. 2013 Feb;99(2):484-9. doi: 10.1016/j.fertnstert.2012.10.026. Epub 2012 Nov 13.

Abstract

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.

MeSH terms

  • Adolescent
  • Adult
  • Female
  • France / epidemiology
  • Genetic Markers / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Genetic Variation / genetics*
  • Humans
  • Polymorphism, Single Nucleotide / genetics*
  • Prevalence
  • Primary Ovarian Insufficiency / epidemiology*
  • Primary Ovarian Insufficiency / genetics*
  • Risk Factors
  • Steroidogenic Factor 1 / genetics*
  • Young Adult

Substances

  • Genetic Markers
  • NR5A1 protein, human
  • Steroidogenic Factor 1