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

A Rampazzo, A Nava, S Malacrida, G Beffagna… - The American Journal of …, 2002 - cell.com
A Rampazzo, A Nava, S Malacrida, G Beffagna, B Bauce, V Rossi, R Zimbello, B Simionati…
The American Journal of human genetics, 2002cell.com
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 …
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.
cell.com