Mutation in human desmoplakin domain binding to plakoglobin causes a dominant form of arrhythmogenic right ventricular cardiomyopathy
- PMID: 12373648
- PMCID: PMC385098
- DOI: 10.1086/344208
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.
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References
Electronic-Database Information
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- ARVDnet, http://telethon.bio.unipd.it/ARVDnet/ (for list of desmoplakin primers used for amplifications and sequencing)
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- GenBank, http://www.ncbi.nlm.nih.gov/Genbank/ (for DSP [accession no. M77830])
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- Human Genome Browser, http://genome.cse.ucsc.edu/index.html (April 2002 issue) (for assessing marker order and intermarker physical distances on chromosome 6)
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- Primer3, http://www-genome.wi.mit.edu/cgi-bin/primer/primer3_www.cgi (for designing PCR primers)
References
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- Armstrong DK, McKenna KE, Purkis PE, Green KJ, Eady RA, Leigh IM, Hughes AE (1999) Haploinsufficiency of desmoplakin causes a striate subtype of palmoplantar keratoderma. Hum Mol Genet 8:143–148 - PubMed
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- Carvajal-Huerta L (1998) Epidermolytic palmoplantar keratoderma with woolly hair and dilated cardiomyopathy. J Am Acad Dermatol 39:418–421 - PubMed
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