Multiple epiphyseal dysplasia (MED) and pseudoachondroplasia (PSACH) are autosomal dominant forms of short-limbed dwarfism (Briggs et al., 1995). Ultrastructural studies on the cartilage of people afflicted with one of the diseases show an accumulation of material within the rough endoplasmic reticulum of the chondrocytes (Maynard et al., 1972; Stanescu et al., 1993). The presence of this material suggests that these disorders may result from a defect in a structural protein of the cartilage (Briggs et al., 1995). Linkage studies in a large family with MED identified a locus for the disease (Oehlmann et al., 1994), contained within the PSACH interval, suggesting that these were allelic disorders. A candidate region was identified that corresponded to the chromosomal location of cartilage oligomeric matrix protein (COMP). Mutations were identified in MED and PSACH patients within the region of the chromosome that corresponded to the COMP gene sequence, thus correlating mutations within this gene to the cartilage disorders MED and PSACH.
A larger investigation is underway to elucidate the development of osteoarthritis in people affected with these chondrodysplasias resulting from mutation in COMP. (Abstract shortened by UMI.)
