title: NR5A1 (SF-1) mutations are not a major cause of primary ovarian insufficiency.
abstract: BACKGROUND
  Primary ovarian insufficiency (POI) is a disorder affecting approximately 1% of women under the age of 40 years. NR5A1 (SF-1) mutations have been recently reported in association with POI.
  
  
  OBJECTIVE
  Our objective was to evaluate the frequency and functional impact of NR5A1 variants in POI.
  
  
  METHODS
  One hundred eighty patients diagnosed with idiopathic POI were screened for NR5A1 mutations and functional analysis was performed for the identified variants. The DNA-binding capacity of the variants was evaluated by means of EMSA, while their transcriptional activity was assessed using luciferase reporter assays.
  
  
  RESULTS
  Sequencing the NR5A1 gene revealed 4 missense variants in 3 patients. These patients were aged 20, 25, and 33 years at diagnosis and presented with secondary amenorrhea. None of them presented a syndromic form, although 2 had a familial history of POI. The functional analysis carried out for these missense variants showed no significant difference in DNA binding capacity or in transcriptional activity compared to wild-type NR5A1.
  
  
  CONCLUSIONS
  Our study in a large cohort of patients with POI showed the prevalence of NR5A1 mutations to be low (1.6%, upper 95% confidence interval 3.5%). Moreover, no functional impact was observed. Overall, in contrast with the initial report, our results exclude NR5A1 mutations as a major genetic cause of POI.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche S693, Université Paris Sud, Faculté de Médecine Paris Sud, F-94276 Le Kremlin-Bicêtre, Paris, France.
authors.forename: Adela
authors.initials: A
authors.lastname: Voican
authors.forename: Anne
authors.initials: A
authors.lastname: Bachelot
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bouligand
authors.forename: Bruno
authors.initials: B
authors.lastname: Francou
authors.forename: Jérôme
authors.initials: J
authors.lastname: Dulon
authors.forename: Marc
authors.initials: M
authors.lastname: Lombès
authors.forename: Philippe
authors.initials: P
authors.lastname: Touraine
authors.forename: Anne
authors.initials: A
authors.lastname: Guiochon-Mantel
mesh_terms: D000328:Adult; D000352:Africa, Northern; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D015331:Cohort Studies; D005060:Europe; D005192:Family Health; D005260:Female; D017930:Genes, Reporter; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D016649:Primary Ovarian Insufficiency / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D011994:Recombinant Proteins / Q000378:metabolism; D015203:Reproducibility of Results; D016415:Sequence Alignment; D054339:Steroidogenic Factor 1 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: C515057:NR5A1 protein, human; D011994:Recombinant Proteins; D054339:Steroidogenic Factor 1