title: Mutation analysis of the inhibin alpha gene in a cohort of Italian women affected by ovarian failure.
abstract: BACKGROUND
  Premature ovarian failure (POF) is a secondary hypergonadotrophic amenorrhoea affecting 1-3% of females, whose aetiology is almost unknown. However, inhibin alpha gene (INHalpha) has recently been indicated as candidate in POF pathogenesis.
  
  
  METHODS
  We analysed patients affected by POF (n = 157) for the missense mutation (769G-->A transition) in the exon 2 of the INHalpha gene. The same analysis was carried out on early menopause (EM) (n = 36) and primary amenorrhoea (n = 12) patients.
  
  
  RESULTS
  The incidence of the mutation was significantly more frequent within both POF (7/157, 4.5%) (Fisher's exact test, P = 0.030) and primary amenorrhoea (3/12, 25%) (Fisher's exact test, P < 0.001) patients, compared with the control population of women (0/100), who experienced physiological menopause. No mutation was found in EM patients. Furthermore, the likelihood of finding the mutation was statistically significant in familial (5/65; 7.7%) (Fisher's exact test, P < 0.01) but not in sporadic (2/92; 2.2%) (Fisher's exact test, P = not significant) POF, compared with the control group. The analysis of pedigrees showing the inheritance of the 769G-->A mutation and POF strengthens the concept of the disease heterogeneity, since the POF phenotype was not always associated with the mutation. Moreover, a higher prevalence of the C allele of a single nucleotide polymorphism (129C-->T), located in the 5'-UTR of the INHalpha gene, was observed in POF patients (80.3%) than in the control group (66.7%) (Fisher's exact test, P = 0.014).
  
  
  CONCLUSIONS
  These data strengthen the concept of the INHalpha gene as a candidate for ovarian failure.
authors.affiliation: Department of Biology and Genetics, Medical Faculty, University of Milan, Via Viotti 3/5, 20133 Milan, Italy. anna.marozzi@unimi.it
authors.forename: Anna
authors.initials: A
authors.lastname: Marozzi
authors.forename: C
authors.initials: C
authors.lastname: Porta
authors.forename: W
authors.initials: W
authors.lastname: Vegetti
authors.forename: P G
authors.initials: PG
authors.lastname: Crosignani
authors.forename: M G
authors.initials: MG
authors.lastname: Tibiletti
authors.forename: L
authors.initials: L
authors.lastname: Dalprà
authors.forename: E
authors.initials: E
authors.lastname: Ginelli
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000328:Adult; D000483:Alleles; D000568:Amenorrhea / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D015331:Cohort Studies; D035061:Control Groups; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007265:Inhibins / Q000235:genetics*; D008593:Menopause / Q000235:genetics; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016649:Primary Ovarian Insufficiency / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; C094377:inhibin-alpha subunit; D007265:Inhibins