Identification of a Fourth Locus for Familial Exudative Vitreoretinopathy (EVR4)

Abstract

Abstract: : Purpose: FZD4 was recently identified as the mutated gene causing familial exudative vitreoretinopathy (FEVR) at the EVR1 locus on chromosome 11q. The purpose of this study was to screen this gene in a large family linked to the EVR1 locus (lod score 5.5). Methods: PCR products were generated using genomic DNA from two affected family members with primers designed to amplify the coding sequence of the gene and flanking intronic sequence. The PCR products were screened for mutations by direct sequencing. Genotyping was performed in all available family members using fluorescently labelled microsatellite markers from chromosome 11q. Results: Screening of the EVR1 gene, FZD4, in this family identified no mutation. To investigate this finding further we performed high-resolution genotyping with markers spanning chromosome 11q. Haplotype analysis clearly excluded FZD4 as the mutated gene in this family and identified a candidate region approximately 10 cM centromeric to EVR1. This new region was also shown to be genetically distinct from the EVR3 locus on chromosome 11p. Conclusions: To date three FEVR loci have been mapped: EVR1 on chromosome 11q (FZD4), EVR2 on chromosome Xp (NDP) and EVR3 on chromosome 11p (unidentified). High-resolution genotyping and haplotype analysis excluded FZD4 as the mutated gene in a family previously linked to the EVR1 locus. The gene mutated in this family lies centromeric to the EVR1 locus and is also genetically distinct from the EVR3 locus. This new locus has been designated EVR4 and is the fourth FEVR locus to be described.

Keywords: linkage analysis • retinal development • genetics