ADDITIONAL MUTATIONS OF TYPE-X COLLAGEN CONFIRM COL10A1 AS THE SCHMIDMETAPHYSEAL CHONDRODYSPLASIA LOCUS

Type X collagen is a short chain collagen expressed in hypertrophic ch ondrocytes during bone growth. A 13bp deletion has been shown to segre gate with Schmid metaphyseal chondrodysplasia, an autosomal dominant d isorder of the osseous skeleton, in a targe Mormon kindred. To increas e our understanding of the role type X collagen plays in development w e have used SSCP analysis to identify three additional mutations in pa tients with Schmid metaphyseal chondrodysplasia. Two are frameshift mu tations (1856delC and 1992delCT) and one is a missense mutation (C591R ). Of interest, the apparently unaffected mother of the patient with t he missense mutation is a somatic mosaic for the mutant allele. All th ree mutations are in the carboxy-terminal non-collagenous domain sugge sting that the effect of these mutations is to impair the mutant polyp eptide's ability to participate in chain association and trimer format ion.