CONCENTRATION OF MUTATIONS CAUSING SCHMID METAPHYSEAL CHONDRODYSPLASIA IN THE C-TERMINAL NONCOLLAGENOUS DOMAIN OF TYPE-X COLLAGEN

Schmid metaphyseal chondrodysplasia (SMCD) has previously been shown t o be the result of mutations in the type X collagen gene, COL1OA1. A f urther three mutations have been identified, including two nonsense mu tations (Y268X, W651X) and a frameshift mutation (1856delCC). Each of the 10 SMCD mutations identified to date is within the C-terminal nonc ollagenous domain of type X collagen and three of five deletions initi ated around the same nucleotide. This domain is believed to be involve d in the initiation of collagen trimerization. The concentration of mu tations within this domain is consistent with the hypothesis that the phenotype is the result of a reduction in the level of mature type X c ollagen due to the mutant polypeptide's inability to participate in tr imer formation, although a dominant negative mechanism cannot be disco unted, on the basis of current evidence. (C) 1995 Wiley-Liss, Inc.