Mutation in human desmoplakin domain binding to plakoglobin causes a dominant form of arrhythmogenic right ventricular cardiomyopathy.
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.
Rampazzo
Alessandra
A
Department of Biology, University of Padua, Italy.
Nava
Andrea
A
Malacrida
Sandro
S
Beffagna
Giorgia
G
Bauce
Barbara
B
Rossi
Valeria
V
Zimbello
Rosanna
R
Simionati
Barbara
B
Basso
Cristina
C
Thiene
Gaetano
G
Towbin
Jeffrey A
JA
Danieli
Gian A
GA
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
D003598:Cytoskeletal Proteins; C495294:DSP protein, human; D051180:Desmoplakins; D005819:Genetic Markers; D051185:gamma Catenin