Identification of a Potential Susceptibility Locus for Macular Telangiectasia Type 2
Year of Publication
Parmalee, NL; Schubert, C; Figueroa, M; Bird, AC; Peto, T; Gillies, MC; Bernstein, PS; Kiryluk, K; Terwilliger, JD; Allikmets, R; The MacTel Project
Cohort Studies Family Health Female Genes-Dominant; DNA; Genetic Linkage Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Haplotypes; Humans; Lod Score; Pedigree; Recombination; Vision Disorders/genetics
Macular Telangiectasia type 2 (MacTel) is a relatively rare macular disease of adult onset presenting with distortions in the visual field and leading to progressive loss of visual acuity. For the purpose of a gene mapping study, several pedigrees were ascertained with multiple affected family members. Seventeen families with a total of 71 individuals (including 45 affected or possibly affected) were recruited at clinical centers in 7 countries under the auspices of the MacTel Project. The disease inheritance was consistent with autosomal dominant segregation with reduced penetrance. Genome-wide linkage analysis was performed, followed by analysis of recombination breakpoints. Linkage analysis identified a single peak with multi-point LOD score of 3.45 on chromosome 1 at 1q41-42 under a dominant model. Recombination mapping defined a minimal candidate region of 15.6 Mb, from 214.32 (rs1579634; 219.96 cM) to 229.92 Mb (rs7542797; 235.07 cM), encompassing the 1q41-42 linkage peak. Sanger sequencing of the top 14 positional candidates genes under the linkage peak revealed no causal variants in these pedigrees.