title: Unique epidermolytic bullous dermatosis with associated lethal cardiomyopathy related to novel desmoplakin mutations.
abstract: BACKGROUND
  Desmoplakin plays a vital role in cell adhesion, linking the transmembrane desmosomal complex to the cytoskeletal network. Clues to the biological significance of desmoplakin have emerged from the embryonic lethal phenotype of null mice and from naturally occurring human desmoplakin mutations, which cause cardiocutaneous phenotypes. INDEX CASE: In this study, we describe a child who presented with the unique constellation of bullous dermatosis, profound plantar keratoderma, alopecia totalis and cardiomyopathy leading to sudden cardiac death at the age of 9 years.
  
  
  RESULTS
  This complex cardiocutaneous phenotype is associated with compound heterozygosity for two novel nonsense desmoplakin mutations. Histological examination of a plantar skin biopsy showed full thickness epidermal acantholysis with superimposed spongiosis, hyperorthokeratosis and focal parakeratosis. Immunohistochemistry and quantitative confocal microscopy showed abnormal tissue distribution and reduced levels of expression for plakoglobin, desmoplakin and connexin 43 at epidermal junctional sites.
  
  
  CONCLUSIONS
  Interpretation of the changes in the context of the two mutations provides insight into the mechanism of clinical cell adhesion disease.
authors.affiliation: Department of Medicine, The Heart Hospital, University College London, University College London Hospitals Trust, London, UK.
authors.forename: Angeliki
authors.initials: A
authors.lastname: Asimaki
authors.forename: Petros
authors.initials: P
authors.lastname: Syrris
authors.forename: Deirdre
authors.initials: D
authors.lastname: Ward
authors.forename: Luis G
authors.initials: LG
authors.lastname: Guereta
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Saffitz
authors.forename: William J
authors.initials: WJ
authors.lastname: McKenna
mesh_terms: D000505:Alopecia / Q000150:complications / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D009202:Cardiomyopathies / Q000150:complications / Q000235:genetics* / Q000473:pathology; D002648:Child; D016757:Death, Sudden, Cardiac / Q000209:etiology; D051180:Desmoplakins / Q000235:genetics*; D004820:Epidermolysis Bullosa / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007645:Keratoderma, Palmoplantar / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction
chemical_list: D051180:Desmoplakins