LINKAGE MAPPING OF THIEL-BEHNKE CORNEAL-DYSTROPHY (CDB2) TO CHROMOSOME 10Q23-Q24

Corneal dystrophy of the anterior basement membrane is a heterogeneous set of diseases characterized by painful, recurrent, bilateral erosio ns of the cornea, which often result in significant visual impairment, There are several similar but clinically distinct: forms of anterior basement membrane/Bowman's membrane disease, including two autosomal d ominant forms, Reis-Bucklers and Thiel-Behnke corneal dystrophy. Genes causing autosomal, nonsyndromic corneal dystrophy have been mapped to human chromosomes Ip, 5q, 12q, 16q, 17p, and 20p. Using microsatellit e markers closely linked to the known corneal dystrophy loci, we exclu ded linkage between the known sites and the disease locus in a large, four-generation family with Thiel-Behnke corneal dystrophy. A genome-w ide search using a panel of microsatellite markers demonstrated a maxi mum two-point lod score of 4.0 at 0% recombination between the disease locus in this family and the marker D10S1239, which maps to 10q23-q24 . Testing with additional microsatellite markers from 10q places the d isease locus between D10S677 and D10S1671, a distance of approximately 12.0 cM, with a maximum multipoint lod score of 5.5, Based on this ev idence, we have identified another locus (CDB2) for corneal dystrophy of the anterior basement membrane/Bowman's membrane, Thiel-Behnke hype , further demonstrating the exceptional genetic and phenotypic heterog eneity of these diseases. (C) 1997 Academic Press.