University of Groningen. Epidermolysis bullosa simplex Bolling, Maria

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1 University of Groningen Epidermolysis bullosa simplex Bolling, Maria IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2010 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Bolling, M. C. (2010). Epidermolysis bullosa simplex: new insights in desmosomal cardiocutaneous syndromes Groningen: s.n. Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date:

2 Epidermolysis bullosa simplex New insights in desmosomal cardiocutaneous syndrome Marieke Bolling, 2010

3 Copyright 2010 by M.C. Bolling, Groningen, The Netherlands Cover design: Marten Faber, Page lay-out: Proefschriftmaken.nl Printed by: Boxpress BV, Oisterwijk Financial support for the publication of this thesis was provided by: Abbott BV; Afdeling Dermatologie Groningen; Astellas Pharma Inc; Fagron BV; Galderma; GlaxoSmithKline; Graduate School of Medicine Groningen; Janssen-Cilag BV; LEO Pharma BV; Louis Widmer Nederland; Medeco; Medizorg; Mölnycke Healthcare BV; Novartis Pharma BV; Roche; Schering-Plough; Stichting Studiefonds Dermatologie; University of Groningen (Rijksuniversiteit Groningen); Universitair Medisch Centrum Groningen (UMCG); Wyeth. The financial support by the J.P. Nater Foundation and Stichting Vlinderkind ( for part of the research described in this thesis is gratefully acknowledged.

4 Epidermolysis bullosa simplex New insights in desmosomal cardiocutaneous syndromes Proefschrift ter verkrijging van het doctoraat in de Medische Wetenschappen aan de Rijksuniversiteit Groningen op gezag van de Rector Magnificus, dr. F. Zwarts, in het openbaar te verdedigen op woensdag 21 april 2010 om uur door Maria Caroline Bolling geboren op 7 juni 1980 te Gouda

5 Promotor: Prof. dr. M.F. Jonkman Beoordelingscommissie: Prof. dr. M.P. van den Berg Prof. dr. W.H.I. McLean Prof. dr. R.J. Sinke ISBN:

6 To the people in my heart I ve got you under my skin, Je t ai dans ma peau

7 Paranimfen: P.C. van den Akker A.M.G. Pasmooij

8 Contents List of abbreviations 9 Chapter 1 Introduction 13 Aim and outline of the thesis 37 Chapter 2 Mutations in KRT5 and KRT14 cause basal 57 epidermolysis bullosa simplex in 75% of the patients Chapter 3 Plectin mutations in basal epidermolysis bullosa 81 simplex with wild-type KRT5 and KRT14 genes Chapter 4 A novel mutation in the L12 domain of keratin 1 is 99 associated with mild epidermolytic ichthyosis Chapter 5 Chromosomal microdeletion explains extracutaneous 111 features in a in a patient with the monogenic genodermatosis Kindler syndrome Chapter 6 Skin and heart: une liaison dangereuse 127 Chapter 7 PLEC1 mutations underlie adult-onset dilated 159 cardiomyopathy in epidermolysis bullosa simplex with muscular dystrophy Chapter 8 Lethal acantholytic epidermolysis bullosa simplex due 171 to a novel homozygous mutation in DSP: expanding the phenotype and implications for desmoplakin function in skin and heart Chapter 9 Discussion and future perspectives 189 Summary 231 Nederlandse samenvatting (Dutch summary) 247 Dankwoord/Acknowledgements 267 List of publications 273 7

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10 List of abbreviations List of abbreviations ABD acgh AD ARVC ALVC bp β4 BMZ cdna Cx43 DCCS DCM DDD DEB DNA DP Dsc Dsg EB EBS EBS-AR EBS-DM EBS-loc EBS-migr EBS-MP ECG EI EM FA FFH-1 fs gdna ICS ID IDP IF actin-binding domain array comparative genomic hybridisation autosomal dominant arrhythmogenic right ventricular cardiomyopathy arrhythmogenic right ventricular cardiomyopathy basepair β4 integrin subunit of integrin α6β4 basement membrane zone coding DNA connexin-43 desmosomal cardio-cutaneous syndrome dilated cardiomyopathy Dowling-Degos Disease dystrophic epidermolysis bullosa deoxyribonucleic acid desmoplakin desmocollin desmoglein epidermolysis bullosa epidermolysis bullosa simplex epidermolysis bullosa simplex autosomal recessive epidermolysis bullosa simplex Dowling Meara epidermolysis bullosa simplex localized epidermolysis bullosa simplex with migratory circinate erythema epidermolysis bullosa simplex with mottled pigmentation electrocardiogram epidermolytic ichthyosis electron microscopy focal adhesion fermitin family homologue-1 frameshift genomic DNA intercellular substance intercalated disc inner dense plaque intermediate filament 9

11 List of abbreviations JEB junctional epidermolysis bullosa K1 keratin 1 K5 keratin 5 K10 keratin 10 K14 keratin 14 KS Kindler syndrome LAEB lethal acantholytic epidermolysis bullosa MD muscular dystrophy NFJS Naegeli Franceschetti Jadassohn Syndrome ODP outer dense plaque OMIM Online Mendelian Inheritance in Man PA pyloric atresia PCR polymerase chain reaction PG plakoglobin PKP plakophilin PPK palmoplantar keratoderma PTC premature termination codon PV pemphigus vulgaris RNA ribonucleic acid SF-EDS skin fragility - ectodermal dysplasia syndrome SF-WH skin fragility - woolly hair syndrome SNP single nucleotide polymorphism SR spectrin-repeat BP180 type XVII collagen WPW Wolff Parkinson White syndrome 10

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