Novel mutations of the cartilage oligomeric matrix protein (COMP) gene in two Japanese patients with pseudoachondroplasia.

Mutations in the cartilage oligomeric matrix protein (COMP) gene cause two skeletal dysplasias, pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED), which are autosomal dominant disorders characterized by short-limb dwarfism. We report novel mutations of the COMP gene identified in two sporadic Japanese cases of PSACH. One had a novel single base substitution in exon 9, resulting in a missense mutation of Gly309Arg in the second type 3 repeat of COMP protein. The other patient had no mutations in any of the exonic sequences of the gene, but she did have a novel base substitution in intron 13. Although this mutation was not located in the conserved sequences for splicing donor and acceptor sites, it might disturb the precise splicing of the COMP transcripts, resulting in the production of abnormal protein with defective last type 3 repeat and/or C-terminal domain.