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N. L. Parmalee, C. Schubert, C. Toomes, J. Merriam, M. Gillies, R. Allikmets, The MacTel Project; Genetic Studies of Macular Telangiectasia. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2814.
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© ARVO (1962-2015); The Authors (2016-present)
Macular telangiectasia type 2 (MacTel) is a relatively rare retinal disease characterized by the presence of telangiectatic vessels, loss of macular pigment, and, eventually, vision. Since familial aggregation suggests a strong genetic component in this disease, this study was undertaken to find the causal gene(s) for MacTel.
Samples were collected from 202 MacTel patients, including 36 individuals in 15 families. Candidate genes were identified based on function in angiogenesis and macular pigment transport, differential expression in retinal vessels, and from known genes in diseases with similar phenotype. Probands from 8 families were screened for variants in the APJ, Apelin, FZD4, NDP, LRP5, DKK1, ANG1, TIE2, VLDLR, and GSTP1 genes by direct sequencing; if applicable, segregation analyses were performed in families and variant frequencies determined by Taqman assays.
Six missense variants were found in 4 genes: Tie2, LRP5, FZD4 and GSTP1. Of those, the P33S variant in FZD4 had been described before as causal in FEVR. This variant was identified in one MacTel patient in another study and subsequently found in four patients in our cohort. However, this variant did not segregate with the disease in MacTel families and was detected in 2-3% of the general population of Caucasian origin. Therefore, the P33S variant was excluded as a possibly causal mutation in both MacTel and FEVR. The Tie2, LRP5 and GSTP1 variants also did not segregate with disease in the families.
No apparent disease-associated mutations were found in ten screened candidate genes for MacTel. However, some of these variants are under further evaluation for potential modifying effects. Candidate gene screening and genome-wide linkage and association studies are underway.
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