THE FATE OF CARTILAGE OLIGOMERIC MATRIX PROTEIN IS DETERMINED BY THE CELL-TYPE IN THE CASE OF A NOVEL MUTATION IN PSEUDOACHONDROPLASIA

We have identified a novel missense mutation in a pseudoachondroplasia (PSACH) patient in one of the type III repeats of cartilage oligomeri c matrix protein (COMP), Enlarged lamellar rough endoplasmic reticulum vesicles were shown to contain accumulated COMP along with type IX co llagen, a cartilage-specific component. COMP was secreted and assemble d normally into the extracellular matrix of tendon, demonstrating that the accumulation of COMP in chondrocytes was a cell-specific phenomen on. We believe that the intracellular storage of COMP causes a nonspec ific aggregation of cartilage-specific molecules and results in a cart ilage matrix deficient in required structural components leading to im paired cartilage growth and maintenance, These data support a common p athogenetic mechanism behind two clinically related chondrodysplasias, PSACH and multiple epiphyseal dysplasia.