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 erosions 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 dominant forms, Reis-Bücklers and Thiel-Behnke corneal dystrophy. Genes causing autosomal, nonsyndromic corneal dystrophy have been mapped to human chromosomes 1p, 5q, 12q, 16q, 17p, and 20p. Using microsatellite markers closely linked to the known corneal dystrophy loci, we excluded linkage between the known sites and the disease locus in a large, four-generation family with Thiel-Behnke corneal dystrophy. A genome-wide search using a panel of microsatellite markers demonstrated a maximum 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 disease locus between D10S677 and D10S1671, a distance of approximately 12.0 cM, with a maximum multipoint lod score of 5.5. Based on this evidence, we have identified another locus (CDB2) for corneal dystrophy of the anterior basement membrane/Bowman's membrane, Thiel-Behnke type, further demonstrating the exceptional genetic and phenotypic heterogeneity of these diseases.