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, whic h has been previously linked to the Kidd blood group. Design: Clinical evaluation with the assessment of visual acuity, color vis ion, and optic nerve appearance to determine affection status. Linkage anal ysis using polymorphic DNA markers. Results: Visual acuities ranged from 20/20 to 6/200. Although linkage was e xcluded for chromosome 3q28-29, markers from chromosome 18 in the vicinity of the Kidd locus were linked to the disorder (D18S34 [maximal lod score (l od(max)) of 5.38 at recombination fraction (theta) of 0.14], D18S548 [lod(m ax) = 7.26, theta = 0.09], D18S861 [lod(max) = 5.32, theta = 0.07], and D18 S479 [lod(max) = 3.28, theta = 0.12:]). Multipoint linkage analysis demonst rated lod scores of greater than 3 in an approximately 3-centimorgan region flanked by D18S34 and D18S479, using 98% penetrance and a phenocopy rate o f 1/50. Conclusions: Dominant optic atrophy is genetically heterogeneous, with loci assigned to chromosomes 3q28-29 and 18q12.2-12.31 Dominant optic atrophy l inked to 18q shows intrafamilial variation similar to that previously repor ted in families linked to 3q, with visual acuities ranging from normal to l egal blindness. The overall distribution of visual acuities appears more fa vorable with the 18q phenotype. Both phenotypes appear to have a similar ra te of visual decline.