Fransiska Malfait, M.D., is a research fellow from the Scientific Foundation, Flanders and a Ph.D. candidate in the Centre for Medical Genetics, Ghent University. Her research interests include the study of genetic defects in the Ehlers-Danlos syndrome.
Molecular genetics in classic Ehlers–Danlos syndrome
Article first published online: 8 NOV 2005
Copyright © 2005 Wiley-Liss, Inc.
American Journal of Medical Genetics Part C: Seminars in Medical Genetics
Special Issue: Connective Tissue Disorders
Volume 139C, Issue 1, pages 17–23, 15 November 2005
How to Cite
Malfait, F. and de Paepe, A. (2005), Molecular genetics in classic Ehlers–Danlos syndrome. Am. J. Med. Genet., 139C: 17–23. doi: 10.1002/ajmg.c.30070
- Issue published online: 18 NOV 2005
- Article first published online: 8 NOV 2005
- The Fund for Scientific Research-Flanders (to Anne De Paepe). Grant Number: G.0090.99N
- classic Ehlers–Danlos syndrome;
- collagen type V;
- genotype–phenotype correlation;
Classic Ehlers–Danlos syndrome is a heritable disorder of connective tissue that is characterized by skin hyperextensibility, fragile and soft skin, delayed wound healing with formation of atrophic scars, easy bruising, and generalized joint hypermobility. Mutations in the COL5A1 and the COL5A2 gene, encoding the α1 and the α2-chain of type V collagen respectively, are identified in approximately 50% of patients with a clinical diagnosis of classic EDS. In approximately one third of patients, the disease is caused by a mutation leading to a non-functional COL5A1 allele, and resulting in haplo-insufficiency of type V collagen. In a smaller proportion of patients, a structural mutation in COL5A1 or COL5A2, resulting in the production of a functionally defective type V collagen protein, is responsible for the phenotype. Inter- and intrafamilial phenotypic variability is observed, but no genotype–phenotype correlations can be made so far. The relatively low mutation detection rate in the COL5A1/A2 genes suggests genetic heterogeneity. Indeed rarely mutations in type I collagen have been identified in patients with classic EDS. Mutations in the gene for tenascin-X have been implicated in an autosomal recessive condition phenotypically overlapping with classic EDS. Several other candidate genes, such as decorin, have emerged from the study of transgenic mouse models with clinical and ultrastructural features reminiscent of classic EDS. However, to date, no human examples have been reported for these mouse models. © 2005 Wiley-Liss, Inc.