Abstract |
Type V collagen mutations are associated with classic Ehlers-Danlos Syndrome (EDS), but it is unknown for which proportion they account and to what extent other genes are involved. We analyzed COL5A1 and COL5A2 in 126 patients with a diagnosis or suspicion of classic EDS. In 93 patients, a type V collagen defect was found, of which 73 were COL5A1 mutations, 13 were COL5A2 mutations and seven were COL5A1 null-alleles with mutation unknown. The majority of the 73 COL5A1 mutations generated a COL5A1 null-allele, whereas one-third were structural mutations, scattered throughout COL5A1. All COL5A2 mutations were structural mutations. Reduced availability of type V collagen appeared to be the major disease-causing mechanism, besides other intra- and extracellular contributing factors. All type V collagen defects were identified within a group of 102 patients fulfilling all major clinical Villefranche criteria, that is, skin hyperextensibility, dystrophic scarring and joint hypermobility. No COL5A1/COL5A2 mutation was detected in 24 patients who displayed skin and joint hyperextensibility but lacked dystrophic scarring. Overall, over 90% of patients fulfilling all major Villefranche criteria for classic EDS were shown to harbor a type V collagen defect, which indicates that this is the major--if not only--cause of classic EDS.
|
Authors | Sofie Symoens, Delfien Syx, Fransiska Malfait, Bert Callewaert, Julie De Backer, Olivier Vanakker, Paul Coucke, Anne De Paepe |
Journal | Human mutation
(Hum Mutat)
Vol. 33
Issue 10
Pg. 1485-93
(Oct 2012)
ISSN: 1098-1004 [Electronic] United States |
PMID | 22696272
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | © 2012 Wiley Periodicals, Inc. |
Chemical References |
- COL5A1 protein, human
- Collagen Type V
|
Topics |
- Collagen Type V
(genetics, metabolism)
- DNA Mutational Analysis
(methods)
- Ehlers-Danlos Syndrome
(diagnosis, genetics)
- Humans
- Mutation
- Skin
(pathology)
|