title: Mutations and sequence variants in GDF9 and BMP15 in patients with premature ovarian failure.
abstract: OBJECTIVE
  Mutations in bone morphogenic protein 15 (BMP15) and growth/differentiation factor 9 (GDF9) lead to altered fertility in animal models. In the human, a heterozygous point mutation of BMP15 has been associated with premature ovarian failure (POF).
  
  
  METHODS
  We have directly sequenced both genes in a cohort of 203 POF patients presenting with primary or secondary amenorrhea and high FSH levels and in a control population including 54 women with regular menstrual cycles who had at least one child.
  
  
  RESULTS
  We have identified several heterozygous variants. One alteration in GDF9 (S186Y) and one in BMP15 (L148P) may have pathogenic effects as both positions are conserved in vertebrate species, ranging from the chicken to mammals. These variants were absent in the control samples. We also found synonymous and neutral substitutions.
  
  
  CONCLUSIONS
  We propose that although mutations in BMP15 and GDF9 are not a major cause of ovarian insufficiency, they may be involved in POF.
authors.affiliation: INSERM 709, Genomics and Epigenetics of Placentary Pathology, Hôpital Cochin, Pavillon Baudelocque, 123 Bd de Port Royal, 75014, Paris, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Laissue
authors.forename: Sophie
authors.initials: S
authors.lastname: Christin-Maitre
authors.forename: Philippe
authors.initials: P
authors.lastname: Touraine
authors.forename: Frederique
authors.initials: F
authors.lastname: Kuttenn
authors.forename: Olli
authors.initials: O
authors.lastname: Ritvos
authors.forename: Kristiina
authors.initials: K
authors.lastname: Aittomaki
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bourcigaux
authors.forename: Laetitia
authors.initials: L
authors.lastname: Jacquesson
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouchard
authors.forename: Rene
authors.initials: R
authors.lastname: Frydman
authors.forename: Didier
authors.initials: D
authors.lastname: Dewailly
authors.forename: Anne-Céline
authors.initials: AC
authors.lastname: Reyss
authors.forename: Luke
authors.initials: L
authors.lastname: Jeffery
authors.forename: Anne
authors.initials: A
authors.lastname: Bachelot
authors.forename: Nathalie
authors.initials: N
authors.lastname: Massin
authors.forename: Marc
authors.initials: M
authors.lastname: Fellous
authors.forename: Reiner A
authors.initials: RA
authors.lastname: Veitia
mesh_terms: D000328:Adult; D000568:Amenorrhea / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D055430:Bone Morphogenetic Protein 15; D015331:Cohort Studies; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005260:Female; D014644:Genetic Variation; D055429:Growth Differentiation Factor 9; D006579:Heterozygote; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: C525901:BMP15 protein, human; D055430:Bone Morphogenetic Protein 15; C525897:GDF9 protein, human; D055429:Growth Differentiation Factor 9; D036341:Intercellular Signaling Peptides and Proteins