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.
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 humandesmoplakin 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: Ryan P Hobbs; Sandra Y Han; Paul A van der Zwaag; Marieke C Bolling; Jan D H Jongbloed; Marcel F Jonkman; Spiro Getsios; Amy S Paller; Kathleen J Green Journal: J Invest Dermatol Date: 2010-07-08 Impact factor: 8.551
Authors: Rita M Cabral; Hong Wan; Clare L Cole; Dominic J Abrams; David P Kelsell; Andrew P South Journal: Cell Tissue Res Date: 2010-06-04 Impact factor: 5.249
Authors: Berivan Baskin; Jon R Skinner; Shubhayan Sanatani; Deborah Terespolsky; Andrew D Krahn; Peter N Ray; Stephen W Scherer; Robert M Hamilton Journal: Hum Genet Date: 2013-06-29 Impact factor: 4.132
Authors: Lynn M Boyden; Chen Y Kam; Angela Hernández-Martín; Jing Zhou; Brittany G Craiglow; Robert Sidbury; Erin F Mathes; Sheilagh M Maguiness; Debra A Crumrine; Mary L Williams; Ronghua Hu; Richard P Lifton; Peter M Elias; Kathleen J Green; Keith A Choate Journal: Hum Mol Genet Date: 2015-11-24 Impact factor: 6.150