Mutations in exon 17B of cartilage oligomeric matrix protein (COMP) cause pseudoachondroplasia

• Published in: Nature genetics Vol. 10; no. 3; pp. 325 - 329
• Main Authors: Hecht, Jacqueline T, Nelson, Laura D, Crowder, Eric, Wang, Yang, Elder, Frederick F.B, Harrison, Wilbur R, Francomano, Clair A, Prange, Christa K, Lennon, Gregory G, Deere, Michelle, Lawler, Jack
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01-07-1995
• Subjects: Achondroplasia - genetics; Base Sequence; Biological and medical sciences; Cartilage - metabolism; Cartilage Oligomeric Matrix Protein; Chromosome Mapping; Chromosomes, Human, Pair 19; Diseases of the osteoarticular system; DNA Primers - genetics; Exons; Extracellular Matrix Proteins; Female; Glycoproteins - genetics; Humans; In Situ Hybridization, Fluorescence; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Matrilin Proteins; Medical sciences; Molecular Sequence Data; Mutation; Pedigree; Point Mutation; Polymorphism, Single-Stranded Conformational; Sequence Deletion; Genetic mapping; Human; Proteins; Cartilage; Gene; Diseases of the osteoarticular system; Genetics; F19-Chromosome; Mutation; Osteochondrodysplasia; Genetic disease; Pseudoachondroplastic spondyloepiphyseal dysplasia
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng0795-325

Pseudoachondroplasia (PSACH) is a well characterized dwarfing condition mapping to chromosome 19p12-13.1. Cartilage oligomeric matrix protein (COMP), a cartilage specific protein, maps to the same location within a contig that spans the PSACH locus. Using single strand conformation polymorphism (SSCP) analysis and nucleotide sequencing we have identified COMP mutations in eight familial and isolated PSACH cases. All mutations involve either a single base-pair change or a three base-pair deletion in exon 17B. Six mutations delete or change a well conserved aspartic acid residue within the calcium-binding type 3 repeats. These results demonstrate that mutations in the COMP gene cause pseudochondroplasia.