title: NR5A1 (SF-1) gene variants in a group of 26 young women with XX primary ovarian insufficiency.
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.
  
  
  METHODS
  Genetic and functional mutation study.
  
  
  METHODS
  University hospitals.
  
  
  METHODS
  Genetic analysis of the NR5A1 gene in 26 XX girls with POI.
  
  
  METHODS
  None.
  
  
  METHODS
  NR5A1 molecular and functional analysis.
  
  
  RESULTS
  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%).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Département d'Hormonologie, Hôpital Lapeyronie, CHU de Montpellier and Université Montpellier 1, Montpellier, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Philibert
authors.forename: Françoise
authors.initials: F
authors.lastname: Paris
authors.forename: Besma
authors.initials: B
authors.lastname: Lakhal
authors.forename: Françoise
authors.initials: F
authors.lastname: Audran
authors.forename: Laura
authors.initials: L
authors.lastname: Gaspari
authors.forename: Ali
authors.initials: A
authors.lastname: Saâd
authors.forename: Sophie
authors.initials: S
authors.lastname: Christin-Maître
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouchard
authors.forename: Charles
authors.initials: C
authors.lastname: Sultan
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D005602:France / Q000453:epidemiology; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D016649:Primary Ovarian Insufficiency / Q000453:epidemiology* / Q000235:genetics*; D012307:Risk Factors; D054339:Steroidogenic Factor 1 / Q000235:genetics*; D055815:Young Adult
chemical_list: D005819:Genetic Markers; C515057:NR5A1 protein, human; D054339:Steroidogenic Factor 1