Br J Ophthalmol 87:1291-1295 doi:10.1136/bjo.87.10.1291
  • Laboratory science - Extended reports

Frizzled 4 gene (FZD4) mutations in patients with familial exudative vitreoretinopathy with variable expressivity

  1. H Kondo1,
  2. H Hayashi1,
  3. K Oshima1,
  4. T Tahira2,
  5. K Hayashi2
  1. 1Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, Japan
  2. 2Division of Genome Analysis, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, Japan
  1. Correspondence to: Hiroyuki Kondo MD, 7-45-1, Nanakuma, Jonan-ku, Fukuoka, Fu 814-0180, Japan; hkondo{at}
  • Accepted 6 February 2003


Aims: 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.

Conclusion:FZD4 gene mutations were found in some cases of autosomal dominant and sporadic FEVR. FZD4 mutations were responsible for FEVR with variable clinical manifestations.