title: Autosomal dominant familial exudative vitreoretinopathy in two Japanese families with FZD4 mutations (H69Y and C181R).
abstract: BACKGROUND
  Familial exudative vitreoretinopathy (FEVR) is a hereditary disorder characterized by impaired vascularization of parts of the peripheral retina. Autosomal dominant FEVR (adFEVR), a major form of FEVR and assigned to chromosome 11q13-23 (EVR1) locus, is caused by deletion mutations in the C- terminal region of the frizzled-4 (FZD4) gene. This paper describes the clinical phenotype of adFEVR in two Japanese families with two different mutations in the FZD4 gene.
  
  
  METHODS
  We encountered three Japanese patients with adFEVR and studied them using mutation analysis of the FZD4 gene with PCR, sequencing, and a restriction enzyme digestion.
  
  
  RESULTS
  Two previously unreported missense mutations, p.H69Y and p.C181R, were identified in the N-terminal extra- cellular region of two of the patients. This region was highly conserved among other vertebrate species and FZD family members, unlike the C-terminal region. Co-segregation analysis revealed that all affected individuals carried one of these mutations, while unaffected individuals did not. The mutations were not detected in normal individuals (n=120). The affected individuals had mild to severe retinal abnormalities.
  
  
  CONCLUSIONS
  FZD4 mutations in either the N- or C-terminal region underlie adFEVR, which indicates that FZD4 plays an important role in retinal angiogenesis. Analysis of FZD4 mutations in families with adFEVR is useful for genetic counseling and for early diagnosis
authors.affiliation: Department of Ophthalmology Jikei University School of Medicine 3-25-8, Nishi-shinbashi, Minato-ku Tokyo 105-8461 Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Omoto
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hayashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Kitahara
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ueoka
mesh_terms: D000595:Amino Acid Sequence; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005122:Exudates and Transudates; D005260:Female; D051157:Frizzled Receptors; D005799:Genes, Dominant; D006801:Humans; D007223:Infant; D007564:Japan; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D017386:Sequence Homology, Amino Acid; D018630:Vitreoretinopathy, Proliferative / Q000175:diagnosis / Q000235:genetics*; D014822:Vitreous Body / Q000473:pathology*
chemical_list: C402930:FZD4 protein, human; D051157:Frizzled Receptors; D011506:Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled