The role of Frizzled-4 mutations in familial exudative vitreoretinopathy and Coats disease.

[coats disease]

The aim of this study is to assess the role of Frizzled-4 (FZD 4 ) in familial exudative vitreoretinopathy (FEVR ) and Coats disease .Tissue samples were collected for DNA extraction and automated DNA sequencing of the two coding exons of FZD 4 in both directions . Cases carrying a FZD 4 mutation and demonstrating extreme disease severity were selected for direct automated sequencing of all coding exons of LRP 5 , NDP and TSPAN 12 . Clinical data were obtained for the purpose of identifying genotype-phenotype correlations .68 probands were diagnosed as having autosomal dominant or sporadic FEVR . Eleven FZD 4 mutations (five missense , three deletions , one insertion , two nonsense ) were identified . Six of these mutations are novel , and none were found in 346 control chromosomes . In 16 cases of Coats disease , one polymorphism combination was found in two samples : no mutations were detected . No genotype-phenotype correlation emerged . Three severely affected cases with FZD 4 mutations failed to show additional mutations in the three other FEVR genes .The authors identified 12 FEVR probands with FZD 4 mutations . FZD 4 mutation screening can be a useful tool especially in mild or atypical cases of FEVR . Germ-line mutations in FZD 4 do not appear to be a common cause of Coats disease .