Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-3-16
pubmed:abstractText
Desmoplakin (DP) anchors the intermediate filament cytoskeleton to the desmosomal cadherins and thereby confers structural stability to tissues. In this study, we present a patient with extensive mucocutaneous blisters, epidermolytic palmoplantar keratoderma, nail dystrophy, enamel dysplasia, and sparse woolly hair. The patient died at the age of 14 years from undiagnosed cardiomyopathy. The skin showed hyperplasia and acantholysis in the mid- and lower epidermal layers, whereas the heart showed extensive fibrosis and fibrofatty replacement in both ventricles. Immunofluorescence microscopy showed a reduction in the C-terminal domain of DP in the skin and oral mucosa. Sequencing of the DP gene showed undescribed mutations in the maternal and paternal alleles. Both mutations affected exon 24 encoding the C-terminal domain. The paternal mutation, c.6310delA, leads to a premature stop codon. The maternal mutation, c.7964 C to A, results in a substitution of an aspartic acid for a conserved alanine residue at amino acid 2655 (A2655D). Structural modeling indicated that this mutation changes the electrostatic potential of the mutated region of DP, possibly altering functions that depend on intermolecular interactions. To conclude, we describe a combination of DP mutation phenotypes affecting the skin, heart, hair, and teeth. This patient case emphasizes the importance of heart examination of patients with desmosomal genodermatoses.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1523-1747
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
130
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
968-78
pubmed:meshHeading
pubmed-meshheading:19924139-Abnormalities, Multiple, pubmed-meshheading:19924139-Adolescent, pubmed-meshheading:19924139-Dental Enamel, pubmed-meshheading:19924139-Desmoplakins, pubmed-meshheading:19924139-Desmosomes, pubmed-meshheading:19924139-Family Health, pubmed-meshheading:19924139-Fatal Outcome, pubmed-meshheading:19924139-Female, pubmed-meshheading:19924139-Hair, pubmed-meshheading:19924139-Heart Defects, Congenital, pubmed-meshheading:19924139-Heterozygote, pubmed-meshheading:19924139-Humans, pubmed-meshheading:19924139-Keratoderma, Palmoplantar, Epidermolytic, pubmed-meshheading:19924139-Mouth Mucosa, pubmed-meshheading:19924139-Mutation, Missense, pubmed-meshheading:19924139-Nail Diseases, pubmed-meshheading:19924139-Phenotype, pubmed-meshheading:19924139-Protein Structure, Tertiary, pubmed-meshheading:19924139-Skin Abnormalities, pubmed-meshheading:19924139-Tooth Abnormalities
pubmed:year
2010
pubmed:articleTitle
Compound heterozygous desmoplakin mutations result in a phenotype with a combination of myocardial, skin, hair, and enamel abnormalities.
pubmed:affiliation
Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
pubmed:publicationType
Journal Article, Case Reports, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural