Comprehensive molecular analysis demonstrates type V collagen mutations in over 90% of patients with classic EDS and allows to refine diagnostic criteria

Hum Mutat. 2012 Oct;33(10):1485-93. doi: 10.1002/humu.22137. Epub 2012 Jul 5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Collagen Type V / genetics*
  • Collagen Type V / metabolism
  • DNA Mutational Analysis / methods
  • Ehlers-Danlos Syndrome / diagnosis*
  • Ehlers-Danlos Syndrome / genetics*
  • Humans
  • Mutation
  • Skin / pathology


  • COL5A1 protein, human
  • Collagen Type V