A LARGE FAMILY WITH FEATURES OF PSEUDOACHONDROPLASIA AND MULTIPLE EPIPHYSEAL DYSPLASIA - EXCLUSION OF 7 CANDIDATE GENE LOCI THAT ENCODE PROTEINS OF THE CARTILAGE EXTRACELLULAR-MATRIX

We have identified a large family with a dominantly inherited chondrod ysplasia characterized by a waddling gait, short limbs, and early onse t osteoarthritis. The radiographic presentation resembles pseudoachond roplasia in childhood and multiple epiphyseal dysplasia in adults. Ele ctron microscopic examination of cartilage reveals accumulation of mat erial within the rough endoplasmic reticulum similar to that seen in p seudoachondroplasia and the Fairbank type of multiple epiphyseal dyspl asia. By linkage analysis, we have excluded the genes for aggrecan, de corin, hexabrachion (tenascin), type II procollagen, the alpha 1 chain of type XI procollagen, the alpha 1 chain of type IX procollagen, and link protein, candidate genes that encode structural components of th e cartilage extracellular matrix, as the disease locus for this disord er.