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Unique epidermolytic bullous dermatosis with associated lethal cardiomyopathy related to novel desmoplakin mutations
Author(s) -
Asimaki Angeliki,
Syrris Petros,
Ward Deirdre,
Guereta Luis G.,
Saffitz Jeffrey E.,
McKenna William J.
Publication year - 2009
Publication title -
journal of cutaneous pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 75
eISSN - 1600-0560
pISSN - 0303-6987
DOI - 10.1111/j.1600-0560.2008.01112.x
Subject(s) - desmoplakin , palmoplantar keratoderma , pathology , plakoglobin , genodermatosis , desmosome , medicine , spongiosis , biology , hyperkeratosis , genetics , catenin , cell , wnt signaling pathway , gene
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.