LINKAGE STUDIES IN DOMINANT OPTIC ATROPHY, KJER TYPE - POSSIBLE EVIDENCE FOR HETEROGENEITY

Dominant optic atrophy, Kjer type, is an autosomal dominant disorder c ausing progressive loss of visual acuity and colour vision from early childhood. The gene (OPA1) has variable expressivity, a penetrance of 0.98, and the locus has been localised to 3q28-29. We have genotyped n ine British families with the disease using 12 polymorphic microsatell ite markers from this region. Linkage and haplotype analysis shows the OPA1 gene to be located in a 2.3 cM interval between markers D3S1601 and D3S2748. One family showed no evidence of linkage with the chromos ome 3 markers, suggesting for the first time that locus heterogeneity for this disease may exist, although exclusion for linkage is based on unaffected subjects. In addition, analysis of recombinants has enable d us to order the 12 markers along chromosome 3.