title: Clinical characteristics and genetic analysis in women with premature ovarian insufficiency.
abstract: OBJECTIVE
  Premature ovarian insufficiency (POI) is defined as a primary ovarian defect characterized by absent menarche (primary amenorrhea) or premature depletion of ovarian follicles before the age of 40 (secondary amenorrhea) with hypergonadotropism and hypoestrogenism.
  
  
  METHODS
  We studied the clinical, biological, and genetic data related to 50 POI patients with a mean age of menopause of 29 years (94% with secondary amenorrhea, 6% with primary amenorrhea and 15% with a family history of POI). Seventeen patients were affected by endocrine autoimmune diseases, antral follicles were observed in 31 patients by ultrasonography.
  
  
  RESULTS
  Karyotype analysis did not show any abnormality of the X chromosome. No mutation in FSH receptor and GDF-9 genes was reported, while in one patient a variant of BMP-15 gene (A180T) was found. Four patients had fragile X mental retardation 1 gene (FMR1) premutation and one an intermediate sized CGG repeats of the same gene. Two patients with FMR1 premutation were sister and developed secondary amenorrhea at the age of 34 and 37 years. The other two patients presented with oligoamenorrhea at the age of 39 and 34 years. The patient harboured the intermediate sized CGG repeats developed secondary amenorrhea at the age of 33 years.
  
  
  CONCLUSIONS
  The genetic analysis performed on a cohort of patients with POI revealed that 8% had FMR1 premutation and only one patient a previously known variant of BMP-15 gene. No alteration of the karyotype and FSH receptor and GDF-9 genes was evidenced.
authors.affiliation: Department of Endocrinology, Research Center of Excellence AmbiSEN, University of Pisa, Pisa, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Ferrarini
authors.forename: Laura
authors.initials: L
authors.lastname: Russo
authors.forename: Franca
authors.initials: F
authors.lastname: Fruzzetti
authors.forename: Patrizia
authors.initials: P
authors.lastname: Agretti
authors.forename: Giuseppina
authors.initials: G
authors.lastname: De Marco
authors.forename: Antonio
authors.initials: A
authors.lastname: Dimida
authors.forename: Elena
authors.initials: E
authors.lastname: Gianetti
authors.forename: Tommaso
authors.initials: T
authors.lastname: Simoncini
authors.forename: Paolo
authors.initials: P
authors.lastname: Simi
authors.forename: Fulvia
authors.initials: F
authors.lastname: Baldinotti
authors.forename: Elena
authors.initials: E
authors.lastname: Benelli
authors.forename: Enrico
authors.initials: E
authors.lastname: Pucci
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinchera
authors.forename: Paolo
authors.initials: P
authors.lastname: Vitti
authors.forename: Massimo
authors.initials: M
authors.lastname: Tonacchera
mesh_terms: D000328:Adult; D000568:Amenorrhea / Q000150:complications / Q000235:genetics; D001327:Autoimmune Diseases / Q000150:complications; D055430:Bone Morphogenetic Protein 15; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D055429:Growth Differentiation Factor 9 / Q000235:genetics; D006801:Humans; D059785:Karyotype; D007986:Luteinizing Hormone / Q000097:blood; D010388:Pelvis / Q000000981:diagnostic imaging; D016649:Primary Ovarian Insufficiency / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D014463:Ultrasonography
chemical_list: D055430:Bone Morphogenetic Protein 15; D004958:Estradiol; D005640:Follicle Stimulating Hormone; D051860:Fragile X Messenger Ribonucleoprotein 1; D055429:Growth Differentiation Factor 9; D007986:Luteinizing Hormone