A novel type X collagen gene mutation (G595R) associated with Schmid-type metaphyseal chondrodysplasia

Metaphyseal chondrodysplasia of the Schmid type (MCDS) is a skeletal dyspla sia affecting the long bone metaphyses; it is characterized by short statur e, bowlegs, and coxa vara. The spine is generally not involved. Here we rep ort a novel missense mutation of the type X collagen gene in a sporadic cas e of MCDS. The mutation was a heterozygous single base-pair transition of G -to-A at nucleotide 1783, which predicted a substitution of glycine by argi nine at codon 595 (G595R) in the carboxyl-terminal noncollagenous domain. I nterestingly, another mutation of the same codon, in which glycine is subst ituted by glutamic acid (G595E), was previously reported to cause spondylom etaphyseal dysplasia (SMD), another group of skeletal dysplasias with invol vement of the spine in addition to the long tubular bones. The novel G595R mutation identified in the present study supports the concept of type X col lagenopathy.