Autosomal Dominant Familial Exudative Vitreoretinopathy: Further Evidence for Genetic Heterogeneity

Abstract

Abstract: : Purpose: To confirm or refute linkage to either of the existing loci for autosomal dominant FEVR (EVR1 and EVR3) in a new pedigree originating from Mexico. Methods: Genomic DNA samples from 13 family members were typed using fluorescently tagged micro satellite markers spanning 11q13-14 and 11p12-13. Additional genotyping was performed with markers spanning the RP12 locus on 1q31-q32.1, a region to which patients with Retinitis Pigmentosa plus a Coats-like phenotype has been mapped. The resulting PCR products were genotyped using an automated DNA sequencer (ABI 377) and Genescan Analysis 2.0.2 with Genotyper 1.1.1 software to analyse the results. Results were documented by constructing haplotypes across each locus. Results: Haplotype analysis revealed recombinants with all markers spanning the entire region of chromosome 11 including the EVR1 and EVR3 loci. Convincing exclusion of the RP12 locus was again obtained through haplotype analysis with 3 recombinants using a marker tightly linked to the gene. Clinical analysis suggested features typical of FEVR, with deficient peripheral retinal vascularisation as the common phenotype in all affected individuals. Conclusion: Exclusion of the two known loci for autosomal dominant FEVR in this pedigree provides further evidence for genetic heterogeneity in this disease and implies the existence of at least 3 genes responsible for the phenotype. Linkage to the RP12 locus was also excluded in this family.

Keywords: 418 gene mapping • 562 retinal degenerations: hereditary