Both authors have equally contributed to this work.
Comprehensive molecular analysis demonstrates type V collagen mutations in over 90% of patients with classic EDS and allows to refine diagnostic criteria†
Article first published online: 5 JUL 2012
© 2012 Wiley Periodicals, Inc.
Volume 33, Issue 10, pages 1485–1493, October 2012
How to Cite
Symoens, S., Syx, D., Malfait, F., Callewaert, B., De Backer, J., Vanakker, O., Coucke, P. and De Paepe, A. (2012), Comprehensive molecular analysis demonstrates type V collagen mutations in over 90% of patients with classic EDS and allows to refine diagnostic criteria. Hum. Mutat., 33: 1485–1493. doi: 10.1002/humu.22137
Communicated by Reed E. Pyeritz
- Issue published online: 13 SEP 2012
- Article first published online: 5 JUL 2012
- Accepted manuscript online: 13 JUN 2012 03:24PM EST
- Manuscript Accepted: 1 JUN 2012
- Manuscript Received: 9 MAR 2012
- Fund for Scientific Research-Flanders. Grant Number: G.0171.05
- GOA. Grant Number: 12051203
- “Geneskin” consortium of the European Commission. Grant Number: 512117
- Methusalem. Grant Number: 08/01M01108
- type V collagen;
- classic Ehlers–Danlos Syndrome;
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. Hum Mutat 33:1485–1493, 2012. © 2012 Wiley Periodicals, Inc.