Publication:

Mutations in the region encoding the von Willebrand factor A domain of matrilin-3 are associated with multiple epiphyseal dysplasia (2001)

Author(s): Chapman KL, Mortier GR, Chapman K, Loughlin J, Grant ME, Briggs MD

  • : Mutations in the region encoding the von Willebrand factor A domain of matrilin-3 are associated with multiple epiphyseal dysplasia

Abstract: Multiple epiphyseal dysplasia (MED) is a relatively mild and clinically variable osteochondrodysplasia, primarily characterized by delayed and irregular ossification of the epiphyses and early-onset osteoarthritis. Mutations in the genes encoding cartilage oligomeric matrix protein (COMP) and type IX collagen (COL9A2 and COL9A3) have previously been shown to cause different forms of MED (refs. 4-13). These dominant forms of MED (EDM1-3) are caused by mutations in the genes encoding structural proteins of the cartilage extracellular matrix (ECM); these proteins interact with high affinity in vitro. A recessive form of MED (EDM4) has also been reported; it is caused by a mutation in the diastrophic dysplasia sulfate transporter gene (SLC26A). A genomewide screen of family with autosomal-dominant MED not linked to the EDM1-3 genes provides significant genetic evidence for a MED locus on the short arm of chromosome 2 (2p24-p23), and a search for candidate genes identified MATN3 (ref. 18), encoding matrilin-3, within the critical region. Matrilin-3 is an oligomeric protein that is present in the cartilage ECM. We have identified two different missense mutations in the exon encoding the von Willebrand factor A (vWFA) domain of matrilin-3 in two unrelated families with MED (EDM5). These are the first mutations to be identified in any of the genes encoding the matrilin family of proteins and confirm a role for matrilin-3 in the development and homeostasis of cartilage and bone.

Notes: Journal Article United States

  • Short Title: Mutations in the region encoding the von Willebrand factor A domain of matrilin-3 are associated with multiple epiphyseal dysplasia
  • Alternate Journal: Nature genetics
  • Date: 02-07-2001
  • Journal: Nature Genetics
  • Volume: 28
  • Issue: 4
  • Pages: 393-396
  • Publisher: Nature Publishing Group
  • Publication type: Article
  • Bibliographic status: Published

Keywords: Adult Child Chromosomes, Human, Pair 2/genetics DNA Mutational Analysis Extracellular Matrix Proteins/*genetics/metabolism Female Femur Head/pathology/radiography Genetic Markers Humans Knee Joint/pathology/radiography Linkage (Genetics) Lod Score Male Middle Aged *Mutation Osteochondrodysplasias/diagnosis/*genetics Pedigree Physical Chromosome Mapping Polymerase Chain Reaction Polymorphism, Single-Stranded Conformational Protein Structure, Tertiary/genetics von Willebrand Factor/*genetics

Staff

Professor John Loughlin
Prof of Musculoskeletal Research