GENETIC REFINEMENT OF DOMINANT OPTIC ATROPHY (OPA1) LOCUS TO WITHIN A2 CM INTERVAL OF CHROMOSOME 3Q

Autosomal dominant optic atrophy (OPA, MIM 165500) is an eye disease c haracterised by variable optic atrophy and reduction in visual acuity. It has an insidious onset in the first decade of life and is clinical ly highly heterogeneous. It is associated with a centrocecal scotoma o f varying size and density and an acquired blue-yellow dyschromatopsia . Recent studies of three large Danish pedigrees have mapped a gene fo r dominant optic atrophy (OPA1) to a 10 cM region on chromosome 3q, be tween markers D3S1314 and D3S1265 (3q28-qter). Genetic linkage analysi s in five British pedigrees confirms mapping to chromosome 3q28-qter. Haplotype analysis of a seven generation pedigree positions the diseas e causing gene between loci D3S3590 and D3S1305, corresponding to a ge netic distance of 2 cM. This represents a significant linkage refineme nt and should facilitate positional cloning of the disease gene.