The main findings of this thesis were the identification of the underlying genetic mutation and characterization of the clinical phenotype of our 'cold case' patients with epidermolysis bullosa (EB) of the Dutch national EB register. EB represents a group or various hereditary mechanobullous diseases, characterized by fragility of the skin and mucous membranes. An 'EB cold case' means that there is a clinical suspicion that a patient or family has EB, but a molecular diagnosis is lacking. The patients were diagnosed and treated at the Department of Dermatology at the University Medical Center Groningen, which is also the national referral center for both genetic and autoimmune blister diseases in the Netherlands. The research gave us insight into several rare, remarkable phenotypes that were the result of mutations in genes, of which some only recently were discovered to be involved in the etiology of EB. For the identification of gene mutations in our patients we used a Next Generation Sequencing (NGS) EB gene panel test. With this technique simultaneously 33 genes that are related to EB coud be examined. Our group identified a heterozygous ITGB4 mutation associated with an autosomal dominant EB phenotype. Also, we characterized a mottled pigmentation phenotype associated with EXPH5 mutations and illustrated an intermediate generalized EB phenotype with prurigo papules in association with DST mutations. Finally, another study showed various heritability for the DST gene suggesting that PLEC may play a role as a genetic modifier.
|Qualification||Doctor of Philosophy|
|Place of Publication||[Groningen]|
|Publication status||Published - 2018|