A TYPE-X COLLAGEN MUTATION CAUSES SCHMID METAPHYSEAL CHONDRODYSPLASIA

The expression of type X collagen is restricted to hypertrophic chondr ocytes in regions undergoing endochondral ossification, such as growth plates. The precise function of type X collagen is unknown but the ti ssue-specific expression prompted us to examine the gene in hereditary disorders of cartilage and bone growth (osteochondrodysplasias). We h ave identified a 13 base pair deletion in one type X collagen allele s egregating with autosomal dominant Schmid metaphyseal chondrodysplasia in a large Mormon kindred (lod score= 18.2 at theta = 0). The mutatio n produces a frameshift which alters the highly conserved C-terminal d omain of the alpha1 (X) chain and reduces the length of the polypeptid e by nine residues. This mutation may prevent association of the mutan t polypeptide during trimer formation, resulting in a decreased amount of normal protein.