ABNORMALITY OF TYPE-IX COLLAGEN IN A PATIENT WITH DIASTROPHIC DYSPLASIA

There is growing evidence that a spectrum of chondrodysplasias are cau sed by mutations in the gene coding for type II collagen. The basic mo lecular defect in diastrophic dysplasia has not been defined, but it a ppears not to be in collagen type II. Cartilage contains other tissue- specific collagens, types IX, X, and XI, but no mutations have yet bee n found in their genes in clinical disease. Type IX collagen is hypoth esized to play a role in the regulation of type II collagen fibril org anization and structure in cartilage extracellular matrix. In this stu dy, we have examined iliac crest growth cartilage from a patient with diastrophic dysplasia. Although collagen fibrils were markedly increas ed in diameter on transmission electron microscopy, type II collagen a ppeared to be normal biochemically. Type XI collagen was also normal. However, type IX collagen appeared abnormal on sodium dodecyl sulfate polyacrylamide gel electrophoresis with a pronounced excess of the COL 1 domain of the molecule in pepsin extracts. The findings point to an abnormality in structure or metabolism of type IX collagen in diastrop hic dysplasia. (C) 1994 Wiley-Liss, Inc.