title: Spectrum and frequency of FZD4 mutations in familial exudative vitreoretinopathy.
abstract: OBJECTIVE
  Mutations in the frizzled-4 gene (FZD4) have recently been associated with autosomal dominant familial exudative vitreoretinopathy (FEVR) in families linking to the EVR1 locus on the long arm of chromosome 11. The purpose of this study was to screen FZD4 in a panel of 40 patients with FEVR to identify the types and location of mutations and to calculate what proportion of this heterogeneous condition is attributable to FZD4 mutations.
  
  
  METHODS
  PCR products were generated from genomic DNA with primers designed to amplify the coding sequence of FZD4. The PCR products were screened for mutations by single-strand conformational polymorphism-heteroduplex analysis (SSCP-HA) and by direct sequencing.
  
  
  RESULTS
  In total, eight mutations were identified, seven of which were novel. Three were deletions (c957delG, c1498delA, and c1501-1502delCT), one was a nonsense mutation (Q505X), and four were missense mutations (G36D, M105T, M157V, and S497F).
  
  
  CONCLUSIONS
  Eight mutations have been identified in the FZD4 gene in a cohort of 40 unrelated patients with FEVR. This result indicates that FZD4 mutations are responsible for only 20% of FEVR index cases and suggests that the other FEVR loci may account for more cases than previously anticipated.
authors.affiliation: Molecular Medicine Unit, University of Leeds, United Kingdom. c.toomes@leeds.ac.uk
authors.forename: Carmel
authors.initials: C
authors.lastname: Toomes
authors.forename: Helen M
authors.initials: HM
authors.lastname: Bottomley
authors.forename: Sheila
authors.initials: S
authors.lastname: Scott
authors.forename: David A
authors.initials: DA
authors.lastname: Mackey
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Craig
authors.forename: Binoy
authors.initials: B
authors.lastname: Appukuttan
authors.forename: J Timothy
authors.initials: JT
authors.lastname: Stout
authors.forename: Christina J
authors.initials: CJ
authors.lastname: Flaxel
authors.forename: Kang
authors.initials: K
authors.lastname: Zhang
authors.forename: Graeme C M
authors.initials: GC
authors.lastname: Black
authors.forename: Alan
authors.initials: A
authors.lastname: Fryer
authors.forename: Louise M
authors.initials: LM
authors.lastname: Downey
authors.forename: Chris F
authors.initials: CF
authors.lastname: Inglehearn
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D005122:Exudates and Transudates; D005260:Female; D051157:Frizzled Receptors; D005787:Gene Frequency; D020180:Heteroduplex Analysis; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled; D018630:Vitreoretinopathy, Proliferative / Q000235:genetics*
chemical_list: D017931:DNA Primers; C402930:FZD4 protein, human; D051157:Frizzled Receptors; D011506:Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled