A 2ND LOCUS FOR FAMILIAL HIGH MYOPIA MAPS TO CHROMOSOME 12Q

dMyopia, or nearsightedness, is the most common eye disorder worldwide . ''Pathologic'' high myopia, or myopia of less than or equal to -6.00 diopters, predisposes individuals to retinal detachment, macular dege neration, cataract, or glaucoma. A locus for autosomal dominant pathol ogic high myopia has been mapped to 18p11.31. We now report significan t linkage of high myopia to at second locus at the 12q21-23 region in a large German/Italian family. The family had no clinical evidence of connective-tissue abnormalities or glaucoma. The average age at diagno sis of myopia was 5.9 years. The average spherical-component refractiv e error for the affected individuals was -9.47 diopters. Markers flank ing or intragenic to the genes for the 18p locus, Stickler syndromes t ype I and II (12q13.1-q13.3 and 6p21.3), Marfan syndrome (15q21.1), an d juvenile glaucoma (chromosome 1q21-q31) showed no linkage to the myo pia in this family The maximum LOD score with two-point linkage analys is in this pedigree was 3.85 at a recombination fraction of .0010, for markers D12S1706 and D12S327. Recombination events identified markers D12S1684 and D12S1605 as flanking markers that define a 30.1-cM inter val on chromosome 12q21-23, for the second myopia gene. These results confirm genetic heterogeneity of myopia. The identification of this ge ne may provide insight into the pathophysiology of myopia and eye deve lopment.