title: Novel mutation in exon 18 of the cartilage oligomeric matrix protein gene causes a severe pseudoachondroplasia.
abstract: Pseudoachondroplasia (PSACH) is a common skeletal dysplasia characterized by disproportionate short stature, early-onset osteoarthrosis, and dysplasia of the spine, epiphysis, and metaphysis. Multiple epiphyseal dysplasia (MED) is a similar but less severe disorder characterized by dysplasia of the epiphysis. Both disorders are caused by mutations in the cartilage oligomeric matrix protein (COMP) gene. COMP mutations cluster in a region of the gene that encodes calmodulin-like repeats (CLRs) and correlate closely with disease severity. Typically, mutations in exon 13 that composes the seventh CLR produce severe PSACH phenotypes, whereas mutations found elsewhere in the gene produce mild PSACH or MED phenotypes. We have identified a PSACH patient carrying a novel mutation in exon 18 of COMP that composes the C-terminal globular domain. This mutation produced a severe PSACH phenotype with marked short stature and deformities of the spine and extremities. Our results extend the range of disease-causing mutations within the COMP gene and demonstrate the importance of the additional domain of COMP protein in its in vivo function.
authors.affiliation: Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN (The Institute of Physical and Chemical Research), Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Mabuchi
authors.forename: N
authors.initials: N
authors.lastname: Haga
authors.forename: T
authors.initials: T
authors.lastname: Ikeda
authors.forename: N
authors.initials: N
authors.lastname: Manabe
authors.forename: H
authors.initials: H
authors.lastname: Ohashi
authors.forename: Y
authors.initials: Y
authors.lastname: Takatori
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: S
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D000130:Achondroplasia / Q000000981:diagnostic imaging / Q000235:genetics*; D000293:Adolescent; D000595:Amino Acid Sequence; D064236:Cartilage Oligomeric Matrix Protein; D005091:Exons; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics*; D005838:Genotype; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008297:Male; D064235:Matrilin Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D017434:Protein Structure, Tertiary; D011859:Radiography; D017386:Sequence Homology, Amino Acid
chemical_list: D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; C577553:TSP5 protein, human