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- Title
Mutations in the region encoding the von Willebrand factor A domain of matrilin-3 are associated with multiple epiphyseal dysplasia.
- Authors
Chapman, Kathryn L.; Mortier, Geert R.; Chapman, Kay; Loughlin, John; Grant, Michael E.; Briggs, Michael D.
- 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.
- Subjects
EXONS (Genetics); VON Willebrand factor
- Publication
Nature Genetics, 2001, Vol 28, Issue 4, p393
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng573