Chan et al. (1998) obtained growth plate cartilage from a patient with Schmid metaphyseal chondrodysplasia (MCDS; 156500), determined the type of collagen X mutation, and analyzed the expression of mutant and normal type X collagen mRNA and protein. The mutation was found to be a single nucleotide substitution that changed the tyr632 codon (TAC) to a stop codon (TAA). However, analysis of the expression of the normal and mutant allele transcripts in growth plate cartilage by reverse transcription PCR, restriction enzyme mapping, and a single nucleotide primer extension assay demonstrated that only normal mRNA was present. The lack of mutant mRNA is most likely the result of nonsense-mediated mRNA decay, a common fate of transcripts carrying premature termination mutations. Furthermore, no mutant protein was detected by immunoblotting cartilage extracts. The data indicated that a functionally null allele leading to type X collagen haploinsufficiency is the molecular basis of MCDS in this patient.
Bateman et al. (2003) demonstrated that Y632X mutant mRNA underwent nonsense-mediated decay in cartilage tissue but not in noncartilage cells.
