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Laboratory science
Original article
The role of Frizzled-4 mutations in familial exudative vitreoretinopathy and Coats disease
  1. Johane M Robitaille1,
  2. Binyou Zheng1,
  3. Karin Wallace2,
  4. M Jill Beis2,
  5. Cuneyt Tatlidil3,
  6. Jenny Yang1,
  7. Tom G Sheidow4,
  8. Lee Siebert4,
  9. Alex V Levin5,
  10. Wai-Ching Lam6,
  11. Brian W Arthur7,
  12. Christopher J Lyons8,
  13. Elisa Jaakkola9,
  14. Ekaterini Tsilou10,
  15. Charles A Williams11,
  16. Richard Grey Weaver Jr12,
  17. Carol L Shields5,
  18. Duane L Guernsey1
  1. 1Dalhousie University, Halifax, Nova Scotia, Canada
  2. 2IWK Health Centre, Halifax, Nova Scotia, Canada
  3. 3Valley Health Regional Hospital, Kentville, Nova Scotia, Canada
  4. 4University of Western Ontario, London, Ontario, Canada
  5. 5Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
  6. 6University of Toronto, Toronto, Ontario, Canada
  7. 7Queen's University, Kingston, Ontario, Canada
  8. 8University of British Columbia, Vancouver, British Columbia, Canada
  9. 9Oulu University, Oulu, Finland
  10. 10National Eye Institute, Bethesda, Maryland, USA
  11. 11University of Florida, Gainesville, Florida, USA
  12. 12Wake Forest University, Winston-Salem, North Carolina, USA
  1. Correspondence to Dr Johane M Robitaille, IWK Health Centre, Eye Care Team, 5850/5980 University Avenue, PO Box 9700, Halifax, Nova Scotia B3K 6R8, Canada; jrobitai{at}dal.ca

Aim The aim of this study is to assess the role of Frizzled-4 (FZD4) in familial exudative vitreoretinopathy (FEVR) and Coats disease.

Methods Tissue samples were collected for DNA extraction and automated DNA sequencing of the two coding exons of FZD4 in both directions. Cases carrying a FZD4 mutation and demonstrating extreme disease severity were selected for direct automated sequencing of all coding exons of LRP5, NDP and TSPAN12. Clinical data were obtained for the purpose of identifying genotype–phenotype correlations.

Results 68 probands were diagnosed as having autosomal dominant or sporadic FEVR. Eleven FZD4 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 FZD4 mutations failed to show additional mutations in the three other FEVR genes.

Conclusion The authors identified 12 FEVR probands with FZD4 mutations. FZD4 mutation screening can be a useful tool especially in mild or atypical cases of FEVR. Germ-line mutations in FZD4 do not appear to be a common cause of Coats disease.

  • FZD4
  • familial exudative vitreoretinopathy
  • genetics
  • coats disease
  • mutation, retina, embryology and development
  • angiogenesis
  • experimental - laboratory

https://doi.org/10.1136/bjo.2010.190116

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    Aim The aim of this study is to assess the role of Frizzled-4 (FZD4) in familial exudative vitreoretinopathy (FEVR) and Coats disease.

    Methods Tissue samples were collected for DNA extraction and automated DNA sequencing of the two coding exons of FZD4 in both directions. Cases carrying a FZD4 mutation and demonstrating extreme disease severity were selected for direct automated sequencing of all coding exons of LRP5, NDP and TSPAN12. Clinical data were obtained for the purpose of identifying genotype–phenotype correlations.

    Results 68 probands were diagnosed as having autosomal dominant or sporadic FEVR. Eleven FZD4 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 FZD4 mutations failed to show additional mutations in the three other FEVR genes.

    Conclusion The authors identified 12 FEVR probands with FZD4 mutations. FZD4 mutation screening can be a useful tool especially in mild or atypical cases of FEVR. Germ-line mutations in FZD4 do not appear to be a common cause of Coats disease.

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    Footnotes

    • ET is an NIH employee.

    • Funding March of Dimes Birth Defects Foundation: United States; IWK Health Centre: Halifax, Nova Scotia, Canada.

    • Competing interests None.

    • Ethics approval Ethics approval was provided by the IWK Health Centre.

    • Provenance and peer review Not commissioned; externally peer reviewed.