title: Hypogonadotropic Hypogonadism due to Novel FGFR1 Mutations.
abstract: OBJECTIVE
  The underlying genetic etiology of hypogonadotropic hypogonadism (HH) is heterogeneous. Fibroblast growth factor signaling is pivotal in the ontogeny of gonadotropin-releasing hormone neurons. Loss-of-function mutations in FGFR1 gene cause variable HH phenotypes encompassing pubertal delay to idiopathic HH (IHH) or Kallmann syndrome (KS). As FGFR1 mutations are common, recognizing mutations and associated phenotypes may enhance clinical management.
  
  
  METHODS
  Using a candidate gene approach, we screened 52 IHH/KS patients.
  
  
  RESULTS
  We identified three novel (IVS3-1G>C and p.W2X, p.R209C) FGFR1 gene mutations. Despite predictive null protein function, patients from the novel mutation families had normosmic IHH without non-reproductive phenotype.
  
  
  CONCLUSIONS
  These findings further emphasize the great variability of FGFR1 mutation phenotypes in IHH/KS.
authors.forename: Gamze
authors.initials: G
authors.lastname: Akkuş
authors.forename: Leman Damla
authors.initials: LD
authors.lastname: Kotan
authors.forename: Erdem
authors.initials: E
authors.lastname: Durmaz
authors.forename: Eda
authors.initials: E
authors.lastname: Mengen
authors.forename: İhsan
authors.initials: İ
authors.lastname: Turan
authors.forename: Ayça
authors.initials: A
authors.lastname: Ulubay
authors.forename: Fatih
authors.initials: F
authors.lastname: Gürbüz
authors.forename: Bilgin
authors.initials: B
authors.lastname: Yüksel
authors.forename: Tamer
authors.initials: T
authors.lastname: Tetiker
authors.affiliation: Çukurova University Faculty of Medicine, Division of Pediatric Endocrinology, Adana, Turkey, E-mail: ktopaloglu@cu.edu.tr.
authors.forename: A Kemal
authors.initials: AK
authors.lastname: Topaloğlu
mesh_terms: D000293:Adolescent; D000328:Adult; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007006:Hypogonadism / Q000235:genetics* / Q000473:pathology; D007713:Klinefelter Syndrome / Q000235:genetics / Q000473:pathology; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011628:Puberty, Delayed / Q000235:genetics / Q000473:pathology; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*; D055815:Young Adult
chemical_list: C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: FGFR1 mutations; Hypogonadotropic hypogonadism; Kallmann syndrome reduced penetrance.