Epidermolysis bullosa simplex. New insights in desmosomal cardiocutaneous syndromes

Promotie: mw. M.C. Bolling, 14. 45 uur, Academiegebouw, Broerstraat 5, Groningen

Proefschrift: Epidermolysis bullosa simplex. New insights in desmosomal cardiocutaneous syndromes

Promotor(s): prof.dr. M.F. Jonkman

Faculteit: Medische Wetenschappen

Contact: via de persvoorlichters van het UMCG, tel. 050-361 2200, e-mail: voorlichting bvl.umcg.nl

Epidermolysis bullosa simplex. New insights in desmosomal cardiocutaneous syndromes

In this thesis several unusual cases of EB are solved at the molecular level, and the lessons that can be learned from the results are discussed. One of the aims of this thesis was to find the molecular defect in a group of patients with blistering in the upper skin, EB simplex (EBS), in which no mutation was found in the usual EBS-associated genes. We found mutation in plectin to underlie several of the EBS cases. Furthermore, mutations in plectin were found to underlie hereditary cardiac disease (cardiomyopathy). This thesis gives an overview of the genes involved in skin as well as cardiac disease. The skin abnormalities precede cardiac disease (sudden death, cardiac failure) and may therefore provide a warning signal. In this thesis mutations in desmoplakin, an essential protein for cell-cell binding in skin and heart, are confirmed as a cause for an early lethal form of EBS: lethal acantholytic EB, and cardiomyopathy is shown to be part of the syndrome. Finding the underlying molecular defect in these cases makes adequate counselling possible and gives further insight in the relation between the genetic defect and the eventual clinical outcome, thereby offering ideas for future therapeutic interventions.