GENETIC-MAPPING OF A LOCUS FOR MULTIPLE EPIPHYSEAL DYSPLASIA (EDM2) TO A REGION OF CHROMOSOME-I CONTAINING A TYPE IX COLLAGEN GENE

Multiple epiphyseal dysplasia (MED) is a dominantly inherited chondrod ysplasia characterized by mild short stature and early-onset osteoarth rosis. Some forms of MED clinically resemble another chondrodysplasia phenotype, the mild form of pseudoachondroplasia (PSACH). On the basis of their clinical similarities as well as similar ultrastructural and biochemical features in cartilage from some patients, it has been pro posed that MED and PSACH belong to a single bone-dysplasia family. Rec ently, both mild and severe PSACH as well as a form of MED have been l inked to the same interval on chromosome 19, suggesting that they may be allelic disorders. Linkage studies with the chromosome 19 markers w ere carried out in a large family with MED and excluded the previously identified interval. Using this family, we have identified an MED loc us on the short arm of chromosome 1, in a region containing the gene ( COL9A2) that encodes the alpha 2 chain of type IX collagen, a structur al component of the cartilage extracellular matrix.