Multiple epiphyseal dysplasia and pseudoachondroplasia due to novel mutations in the calmodulin‐like repeats of cartilage oligomeric matrix protein

Abstract

A child with a mild form of pseudoachondroplasia was heterozygous for a deletion of 12 nucleotides from exon 10 of the cartilage oligomeric matrix protein (COMP) gene. It resulted in the deletion of valine 513 to lysine 516 from the eighth calmodulin-like repeat of COMP monomers. A child with the Fairbank's type of multiple epiphyseal dysplasia was also heterozygous for a COMP mutation. It substituted cysteine 371 by serine in the fourth calmodulin-like repeat. Both mutations were likely to alter the conformation and calcium binding of the mutant COMP protein chains. These findings support the proposal that deletions and insertions within the calmodulin-like domain produce pseudoachondroplasia, while amino acid substitutions with this domain may produce either pseudoachondroplasia or multiple epiphyseal dysplasia.