The benign concentric annular macular dystrophy (BCAMD) locus maps to 6p12.3–q16

Abstract

Abstract: : Purpose: To describe the clinical findings and to identify the genetic locus in a Dutch family with autosomal dominant benign concentric annular macular dystrophy (BCAMD) Methods: All family members underwent ophthalmic examination. We performed linkage analysis of candidate retinal dystrophy loci and a whole genome scan. Five candidate genes from the linked locus were analyzed for mutations by direct sequencing. Results: The BCAMD phenotype is initially characterized by parafoveal hypopigmentation and a good visual acuity, but progresses to a retinitis pigmentosa–like phenotype. Linkage analysis established complete segregation of the BCAMD phenotype (maximum multipoint LOD score 3.8) with DNA markers at chromosome 6p12.3–q16. Recombination events defined a critical interval spanning 30.7 cM at chromosome 6q between markers D6S269 and D6S300. This interval encompasses several retinal dystrophy loci, including the ELOVL4 gene, mutated in autosomal dominant Stargardt disease and the RIM1 gene, mutated in autosomal dominant cone–rod dystrophy, as well as the retinally expressed GABRR1 & 2 genes. Mutation screening of these four genes revealed no mutations. Sequence analysis of the interphotoreceptor matrix proteoglycan 1 gene, IMPG1, also residing in the BCAMD locus, revealed a single base pair change (T>C) of nucleotide 1866 in exon 13, resulting in a Leu579Pro amino acid substitution. This mutation was absent in 190 control individuals. Conclusions: We found significant linkage for the BCAMD defect with chromosomal region 6p12.3–q16. A Leu579Pro mutation in the IMPG1 gene might play a causal role.

Keywords: linkage analysis • gene screening • macula/fovea