title: The fate of cartilage oligomeric matrix protein is determined by the cell type in the case of a novel mutation in pseudoachondroplasia.
abstract: We have identified a novel missense mutation in a pseudoachondroplasia (PSACH) patient in one of the type III repeats of cartilage oligomeric matrix protein (COMP). Enlarged lamellar rough endoplasmic reticulum vesicles were shown to contain accumulated COMP along with type IX collagen, a cartilage-specific component. COMP was secreted and assembled normally into the extracellular matrix of tendon, demonstrating that the accumulation of COMP in chondrocytes was a cell-specific phenomenon. We believe that the intracellular storage of COMP causes a nonspecific aggregation of cartilage-specific molecules and results in a cartilage matrix deficient in required structural components leading to impaired cartilage growth and maintenance. These data support a common pathogenetic mechanism behind two clinically related chondrodysplasias, PSACH and multiple epiphyseal dysplasia.
authors.affiliation: Research Department, Shriners Hospital for Children, Portland, Oregon 97201, USA.
authors.forename: B K
authors.initials: BK
authors.lastname: Maddox
authors.forename: D R
authors.initials: DR
authors.lastname: Keene
authors.forename: L Y
authors.initials: LY
authors.lastname: Sakai
authors.forename: N L
authors.initials: NL
authors.lastname: Charbonneau
authors.forename: N P
authors.initials: NP
authors.lastname: Morris
authors.forename: C C
authors.initials: CC
authors.lastname: Ridgway
authors.forename: B A
authors.initials: BA
authors.lastname: Boswell
authors.forename: M D
authors.initials: MD
authors.lastname: Sussman
authors.forename: W A
authors.initials: WA
authors.lastname: Horton
authors.forename: H P
authors.initials: HP
authors.lastname: Bächinger
authors.forename: J T
authors.initials: JT
authors.lastname: Hecht
mesh_terms: D000130:Achondroplasia / Q000235:genetics* / Q000473:pathology; D002356:Cartilage; D064236:Cartilage Oligomeric Matrix Protein; D002648:Child; D019902:Chondrocytes / Q000378:metabolism / Q000648:ultrastructure; D002888:Chromosomes, Human, Pair 19; D003094:Collagen / Q000378:metabolism; D018870:Endoplasmic Reticulum, Rough / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D064235:Matrilin Proteins; D016253:Microscopy, Immunoelectron; D009154:Mutation; D017433:Protein Structure, Secondary; D013710:Tendons / Q000378:metabolism
chemical_list: D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; C577553:TSP5 protein, human; D003094:Collagen