Genetic heterogeneity of dominant optic atrophy, Kjer type: Identification of a second locus on chromosome 18q12.2-12.3

Objective: To evaluate a family with autosomal dominant optic atrophy, which has been previously linked to the Kidd blood group. Design: Clinical evaluation with the assessment of visual acuity, color vision, and optic nerve appearance to determine affection status. Linkage analysis using polymorphic DNA markers. Results: Visual acuities ranged from 20/20 to 6/200. Although linkage was excluded for chromosome 3q28-29, markers from chromosome 18 in the vicinity of the Kidd locus were linked to the disorder (D18S34 [maximal lod score (lod(max)) of 5.38 at recombination fraction (θ) of 0.14], D185548 [lod(max) = 7.26, 0 =0.09], D18S861 [lod(max) = 5.32, θ = 0.07], and D18S479 [lod(max) = 3.28, θ = 0.12:]). Multipoint linkage analysis demonstrated lod scores of greater than 3 in an approximately 3- centimorgan region flanked by D18S34 and D18S479, using 98% penetrance and a phenocopy rate of 1/50. Conclusions: Dominant optic atrophy is genetically heterogeneous, with loci assigned to chromosomes 3q28-29 and 18q12.2-12.3. Dominant optic atrophy linked to 18q shows intrafamilial variation similar to that previously reported in families linked to 3q, with visual acuities ranging from normal to legal blindness. The overall distribution of visual acuities appears more favorable with the 18q phenotype. Both phenotypes appear to have a similar rate of visual decline.