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

Am J Hum Genet. 2002 Nov;71(5):1200-6. doi: 10.1086/344208. Epub 2002 Oct 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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


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

Associated data

  • GENBANK/M77830
  • OMIM/107970
  • OMIM/600996
  • OMIM/601214
  • OMIM/602086
  • OMIM/602087
  • OMIM/605676