Additional mutations of type X collagen confirm COL10A1 as the Schmid metaphyseal chondrodysplasia locus.

Type X collagen is a short chain collagen expressed in hypertrophic chondrocytes during bone growth. A 13bp deletion has been shown to segregate with Schmid metaphyseal chondrodysplasia, an autosomal dominant disorder of the osseous skeleton, in a large Mormon kindred. To increase our understanding of the role type X collagen plays in development we have used SSCP analysis to identify three additional mutations in patients with Schmid metaphyseal chondrodysplasia. Two are frameshift mutations (1856delC and 1992delCT) and one is a missense mutation (C591R). Of interest, the apparently unaffected mother of the patient with the missense mutation is a somatic mosaic for the mutant allele. All three mutations are in the carboxy-terminal non-collagenous domain suggesting that the effect of these mutations is to impair the mutant polypeptide's ability to participate in chain association and trimer formation.