Concentration of mutations causing schmid metaphyseal chondrodysplasia in the C-terminal noncollagenous domain of type X collagen

Abstract
Schmid metaphyseal chondrodysplasia (SMCD) has previously been shown to be the result of mutations in the type X collagen gene, COL10A1. A further three mutations have been identified, including two nonsense mutations (Y268X, W651X) and a frameshift mutation (1856delCC). Each of the 10 SMCD mutations identified to date is within the C‐terminal noncollagenous domain of type X collagen and three of five deletions initiated around the same nucleotide. This domain is believed to be involved in the initiation of collagen trimerization. The concentration of mutations within this domain is consistent with the hypothesis that the phenotype is the result of a reduction in the level of mature type X collagen due to the mutant polypcptide's inability to participate in trimer formation, although a dominant‐negative mechanism cannot be discounted, on the basis of current evidence. © Wiley‐Liss, Inc.