Mutation in human desmoplakin domain binding to plakoglobin causes a dominant form of arrhythmogenic right ventricular cardiomyopathy.

Abstract

Arrhythmogenic right ventricular cardiomyopathy (ARVD/C) is a genetically heterogeneous disease characterized by progressive degeneration of the right ventricular myocardium and increased risk of sudden death. Here, we report on a genome scan in one Italian family in which the disease appeared unlinked to any of the six different ARVD loci reported so far; we identify a mutation (S299R) in exon 7 of desmoplakin (DSP), which modifies a putative phosphorylation site in the N-terminal domain binding plakoglobin. It is interesting that a nonsense DSP mutation was reported elsewhere in the literature, inherited as a recessive trait and causing a biventricular dilative cardiomyopathy associated with palmoplantar keratoderma and woolly hairs. Therefore, different DSP mutations might produce different clinical phenotypes, with different modes of inheritance.

• Authors: Alessandra Rampazzo, Andrea Nava, Sandro Malacrida, Giorgia Beffagna, Barbara Bauce, Valeria Rossi, Rosanna Zimbello, Barbara Simionati, Cristina Basso, Gaetano Thiene, Jeffrey A Towbin, Gian A Danieli
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 71 Issue 5 Pg. 1200-6 (Nov 2002) ISSN: 0002-9297 [Print] United States
• PMID: 12373648 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cytoskeletal Proteins
• DSP protein, human
• Desmoplakins
• Genetic Markers
• gamma Catenin

Topics

• Adolescent
• Aged
• Amino Acid Sequence
• Arrhythmogenic Right Ventricular Dysplasia (genetics)
• Cytoskeletal Proteins (genetics, metabolism)
• Desmoplakins
• Female
• Genes, Dominant
• Genetic Markers
• Humans
• Male
• Molecular Sequence Data
• Pedigree
• Point Mutation
• gamma Catenin