Refinement of the locus for autosomal dominant juvenile optic atrophy to a 2 cM region on 3q28.

Juvenile optic atrophy (Kjer type; OPA1) is an autosomal dominant trait with an insidious onset in the first decade of life. The condition is characterized by a progressive loss of visual acuity that usually occurs with severe defects in color vision and visual fields. Genetic linkage analysis of a number of families has already assigned the OPA1 locus to the 3q28-qter region, within an estimated region of about 8 cM that is flanked by D3S1601 and D3S1265. Our study of a four-generation English family also supported tight linkage between the OPA1 locus and a group of DNA markers from the reported region. Of the 13 markers genotyped in this family, D3S2305 provided the maximum LOD score of 3.91 at theta = 0.00. Inspection of the haplotype transmission in this family identified critical recombinant individuals that refined the location of the OPA1 locus to an estimated region of about 2cM that is flanked by two DNA markers of D3S1601 and D3S2748. This refinement should facilitate the molecular cloning of the OPA1 gene and the determination of its defective product.