THE GENE FOR SCHNYDERS CRYSTALLINE CORNEAL-DYSTROPHY MAPS TO HUMAN-CHROMOSOME 1P34.1-P36

Schnyder's crystalline corneal dystrophy (SCCD) is an autosomal domina nt eye disease characterized by a bilateral clouding of the central co rnea, arcus lipoides and/or visible crystalline deposits of cholestero l in the stroma, There is accumulation of phospholipid, unesterified c holesterol and cholesterol ester in the corneal stroma; this is believ ed to be due to an imbalance in the local factors affecting lipid/chol esterol transport or metabolism. The cellular mechanism of abnormal li pid transport and metabolism in SCCD is of interest due to its potenti al involvement in atherosclerosis, and its implications for the pathog enesis of cerebrovascular, coronary and peripheral vascular disease as well as corneal opacification. To determine the chromosomal location of the SCCD locus, genome-wide linkage analysis has been performed in two large Swede-Finn kindreds recently identified in central Massachus etts. After analysing 300 microsatellite markers >90% of the genome wa s excluded from linkage to the SCCD locus. We now report the chromosom al assignment of the gene for SCCD in both families to be 1p34.1-p36; the maximum multipoint led-score was 8.48 in the interval between D1S2 14 and D1S503. From haplotype analysis, the SCCD locus lies in the 16 cM interval between markers D1S2663 and D1S228. Several candidate gene s for SCCD have been localized to the 1p34.1-p36 interval.