title: Frizzled 4 gene (FZD4) mutations in patients with familial exudative vitreoretinopathy with variable expressivity.
abstract: OBJECTIVE
  To search for mutations in the frizzled 4 (FZD4) gene in patients with familial exudative vitreoretinopathy (FEVR) and to delineate the defective gene associated clinical features.
  
  
  METHODS
  Direct sequencing following polymerase chain reaction of exons of FZD4 was performed for 24 probands with FEVR (18 familial and six sporadic), and some of their families. Clinical symptoms among individuals with mutations were assessed.
  
  
  RESULTS
  Four novel mutations were identified in four patients with familial and one with sporadic FEVR. Three of these mutations were missense (M105V, R417Q, and G488D) and one was a nonsense change (W319X). M105V, R417Q, and G488D co-segregated with the disease. None of these sequence changes was found among 300 chromosomes from 150 healthy volunteers. The severity of vitreoretinopathy in the individuals involved in this study varied, but no patient with mutations in FZD4 exhibited rhegmatogenous retinal detachment although this pathology is thought to be the most common type of retinal detachment in FEVR.
  
  
  CONCLUSIONS
  FZD4 gene mutations were found in some cases of autosomal dominant and sporadic FEVR. FZD4 mutations were responsible for FEVR with variable clinical manifestations.
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002675:Child, Preschool; D018389:Codon, Nonsense / Q000235:genetics*; D005122:Exudates and Transudates; D015785:Eye Diseases, Hereditary / Q000235:genetics*; D005260:Female; D051157:Frizzled Receptors; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D012164:Retinal Diseases / Q000235:genetics*; D014822:Vitreous Body
chemical_list: D018389:Codon, Nonsense; C402930:FZD4 protein, human; D051157:Frizzled Receptors; D011506:Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled