title: 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.affiliation: Department of Biology, University of Padua, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rampazzo
authors.forename: Andrea
authors.initials: A
authors.lastname: Nava
authors.forename: Sandro
authors.initials: S
authors.lastname: Malacrida
authors.forename: Giorgia
authors.initials: G
authors.lastname: Beffagna
authors.forename: Barbara
authors.initials: B
authors.lastname: Bauce
authors.forename: Valeria
authors.initials: V
authors.lastname: Rossi
authors.forename: Rosanna
authors.initials: R
authors.lastname: Zimbello
authors.forename: Barbara
authors.initials: B
authors.lastname: Simionati
authors.forename: Cristina
authors.initials: C
authors.lastname: Basso
authors.forename: Gaetano
authors.initials: G
authors.lastname: Thiene
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Towbin
authors.forename: Gian A
authors.initials: GA
authors.lastname: Danieli
mesh_terms: D000293:Adolescent; D000368:Aged; D000595:Amino Acid Sequence; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D051180:Desmoplakins; D005260:Female; D005799:Genes, Dominant; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D051185:gamma Catenin
chemical_list: D003598:Cytoskeletal Proteins; C495294:DSP protein, human; D051180:Desmoplakins; D005819:Genetic Markers; D051185:gamma Catenin