Publication
Title
Mutations in the region encoding the von Willebrand factor A domain of matrilin-3 are associated with multiple epiphyseal dysplasia
Author
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 osteoarthritis1, 2, 3. 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. 413). These dominant forms of MED (EDM13) are caused by mutations in the genes encoding structural proteins of the cartilage extracellular matrix (ECM); these proteins interact with high affinity in vitro14, 15. A recessive form of MED (EDM4) has also been reported; it is caused by a mutation in the diastrophic dysplasia sulfate transporter gene16 (SLC26A). A genomewide screen of family with autosomal-dominant MED not linked to the EDM13 genes17 provides significant genetic evidence for a MED locus on the short arm of chromosome 2 (2p24p23), 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.
Language
English
Source (journal)
Nature genetics. - New York, N.Y.
Publication
New York, N.Y. : 2001
ISSN
1061-4036
Volume/pages
28:4(2001), p. 393-396
ISI
000170174800024
Full text (Publisher's DOI)
UAntwerpen
Faculty/Department
Publication type
Subject
External links
Web of Science
Record
Identification
Creation 05.06.2012
Last edited 18.09.2017