Genetic Analysis of Autosomal Dominant Familial Exudative Vitreoretinopathy: Towards the Identification of a Gene for EVR1

Abstract

Abstract: : Purpose: Familial exudative vitreoretinopathy (FEVR) is a hereditary ocular disorder associated with failure of peripheral retinal vascularization. Severe visual impairment commonly occurs in childhood or teenage years from complications such as macular dragging and retinal detachment. The most common mode of inheritance is autosomal dominant with complete penetrance and variable expressivity, although X-linked recessive and autosomal recessive pedigrees have also been reported. Two gene loci for autosomal dominant FEVR (adFEVR) have been mapped to chromosome 11q13-23 (EVR1) and more recently to chromosome 11p12-13 (EVR3). We are reporting the results of genetic analysis in a large Canadian pedigree with adFEVR. The goal is to identify a gene for adFEVR. Methods: Seventy-five family members (27 affected/48 unaffected) were recruited for genotyping and linkage analysis. The collected data were analysed using the LINKAGE computer programs. The locus identified by linkage analysis was further refined using 19 polymorphic microsatellite markers. Results: Linkage analysis confirmed the locus for adFEVR in this family to coincide with EVR1. The locus was further refined to a 1.2cM region. Candidate genes in the critical region are currently being screened for the presence of mutations. Conclusion: adFEVR in this family maps to a very narrow region coincident with EVR1 on chromosome 11q13-23. Identification of this narrow region enables the identification of the EVR1 gene for this disease in this family by physical mapping and/or candidate gene analysis.

Keywords: 420 genetics • 524 proliferative vitreoretinopathy • 418 gene mapping