Funding sources Italian Ministry of Health (Ricerca corrente RC09).
A founder synonymous COL7A1 mutation in three Danish families with dominant dystrophic epidermolysis bullosa pruriginosa identifies exonic regulatory sequences required for exon 87 splicing
Article first published online: 28 JUL 2011
© 2011 The Authors. BJD © 2011 British Association of Dermatologists
British Journal of Dermatology
Volume 165, Issue 3, pages 678–682, September 2011
How to Cite
Covaciu, C., Grosso, F., Pisaneschi, E., Zambruno, G., Gregersen, P.A., Sommerlund, M., Hertz, J.M. and Castiglia, D. (2011), A founder synonymous COL7A1 mutation in three Danish families with dominant dystrophic epidermolysis bullosa pruriginosa identifies exonic regulatory sequences required for exon 87 splicing. British Journal of Dermatology, 165: 678–682. doi: 10.1111/j.1365-2133.2011.10414.x
Conflicts of interest None declared.
- Issue published online: 28 AUG 2011
- Article first published online: 28 JUL 2011
- Accepted manuscript online: 17 MAY 2011 01:38AM EST
- Accepted for publication 1 May 2011
Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) (OMIM 604129) represents a distinct variant within the DEB clinical spectrum.1 It is characterized by intense pruritus and distinctive nodular prurigo-like and/or hypertrophic lichenoid lesions mainly localized on the arms, legs and upper shoulders.2 DEB-Pr is caused by either dominant (DDEB-Pr) or recessive mutations in the COL7A1 gene encoding type VII collagen (COLVII).3–5 The full spectrum of COL7A1 mutations in DEB-Pr remains elusive and the genotype–phenotype correlation is largely incomplete. Here, we report and functionally characterize a previously unrecognized translationally silent exonic COL7A1 mutation that results in skipping of exon 87 and is associated with DDEB-Pr phenotypes in several members of three apparently unrelated Danish families. A haplotype segregation study suggested a common ancestor in these kindred. Functional splicing analysis of the mutant exon by a COL7A1 minigene construct and computational prediction for splicing regulatory cis-sequences prove that the mutation alters the activity of an exonic splicing enhancer (ESE) critical for exon inclusion.6,7 These findings substantiate for the first time the involvement of an ESE mutation in the pathogenesis of DEB and have implications for genetic counselling of Danish families with DDEB.