title: De novo frameshift mutation in fibroblast growth factor 8 in a male patient with gonadotropin deficiency.
abstract: OBJECTIVE
  Missense, nonsense, and splice mutations in the Fibroblast Growth Factor 8(FGF8) have recently been identified in patients with hypothalamo-pituitary dysfunction and craniofacial anomalies. Here, we report a male patient with a frameshift mutation in FGF8.
  
  
  METHODS
  The patient exhibited micropenis, craniofacial anomalies, and ventricular septal defect at birth. Clinical evaluation at 16 years and 8 months of age revealed delayed puberty, hyposmia, borderline mental retardation, and mild hearing difficulty. Endocrine findings included gonadotropin deficiency and primary hypothyroidism.
  
  
  RESULTS
  Molecular analysis identified a de novo heterozygous p.S192fsX204 mutation in the last exon of FGF8. RT-PCR analysis of normal human tissues detected FGF8 expression in the genital skin, and whole-mount in situ hybridization analysis of mouse embryos revealed Fgf8 expression in the anlage of the penis.
  
  
  CONCLUSIONS
  The results indicate that frameshift mutations in FGF8 account for a part of the etiology of hypothalamo-pituitary dysfunction. Micropenis in patients with FGF8 abnormalities appears to be caused by gonadotropin deficiency and defective outgrowth of the anlage of the penis.
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Erina
authors.initials: E
authors.lastname: Suzuki
authors.forename: Shuichi
authors.initials: S
authors.lastname: Yatsuga
authors.forename: Maki
authors.initials: M
authors.lastname: Igarashi
authors.forename: Mami
authors.initials: M
authors.lastname: Miyado
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakabayashi
authors.forename: Keiko
authors.initials: K
authors.lastname: Hayashi
authors.forename: Kenichirou
authors.initials: K
authors.lastname: Hata
authors.forename: Akihiro
authors.initials: A
authors.lastname: Umezawa
authors.forename: Gen
authors.initials: G
authors.lastname: Yamada
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
authors.forename: Maki
authors.initials: M
authors.lastname: Fukami
mesh_terms: D000293:Adolescent; D000818:Animals; D019465:Craniofacial Abnormalities / Q000235:genetics; D005058:Eunuchism / Q000151:congenital* / Q000235:genetics; D051524:Fibroblast Growth Factor 8 / Q000235:genetics*; D016368:Frameshift Mutation / Q000235:genetics*; D005832:Genital Diseases, Male / Q000235:genetics; D006345:Heart Septal Defects, Ventricular / Q000235:genetics; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics; D008297:Male; D051379:Mice; D023421:Models, Animal; D010413:Penis / Q000002:abnormalities
chemical_list: C496456:FGF8 protein, human; D051524:Fibroblast Growth Factor 8