REFINEMENT OF THE LOCUS FOR AUTOSOMAL-DOMINANT JUVENILE OPTIC ATROPHYTO A 2 CM REGION ON 3Q28

Juvenile optic atrophy (Kjer type; OPAI) is an autosomal dominant trai t with an insidious onset in the first decade of life. The condition i s characterized by a progressive loss of visual acuity that usually oc curs with severe defects in color vision and visual fields. Genetic li nkage analysis of a number of families has already assigned the OPAI l ocus to the 3q28-qter region, within an estimated region of about 8 cM that is flanked by D(3)SI60I and D(3)SI26(5). Our Study of a four-gen eration English family also supported tight linkage between the OPAI l ocus and a group of DNA markers from the reported region. Of the I3 ma rkers genotyped in this family, D(3)S2(3)o(5) provided the maximum LOD score of 3.9I at theta=0.00. Inspection of the haplotype transmission in this family identified critical recombinant individuals that refin ed the location of the OPAI locus to an estimated region of about 2cM that is flanked by two DNA markers of D(3)SI60I and D(3)S2(74)8. This refinement should facilitate the molecular cloning of the OPAI gene an d the determination of its defective product.