Arrhythmogenic Right Ventricular Cardiomyopathy and Desmin: Another gene fits the shoe

Abstract

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is an inherited disease of the heart muscle. The cardiomyopathy manifests as progressive fibrofatty replacement of myocytes, predominantly in the right ventricle. ARVC presents with ventricular arrhythmias and a high incidence of sudden cardiac death. To date, mutations in eight gene loci associated with ARVC have been identified. Five of these loci encode desmosomal proteins [desmoplakin, 1 Rampazzo A. Nava A. Malacrida S. et al. Mutation in human desmoplakin domain binding to plakoglobin causes a dominant form of arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet. 2002; 71: 1200-1206 Abstract Full Text Full Text PDF PubMed Scopus (508) Google Scholar plakophilin-2 (PKP2), 2 Gerull B. Heuser A. Wichter T. et al. Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy. Nat Genet. 2004; 36: 1162-1164 Crossref PubMed Scopus (636) Google Scholar desmoglein-2, 3 Pilichou K. Nava A. Basso C. et al. Mutations in desmoglein-2 gene are associated with arrhythmogenic right ventricular cardiomyopathy. Circulation. 2006; 113: 1171-1179 Crossref PubMed Scopus (447) Google Scholar desmocollin-2, 4 Syrris P. Ward D. Evans A. et al. Arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in the desmosomal gene desmocollin-2. Am J Hum Genet. 2006; 79: 978-984 Abstract Full Text Full Text PDF PubMed Scopus (294) Google Scholar plakoglobin (JUP), 5 Asimaki A. Syrris P. Wichter T. Matthias P. Saffitz J.E. McKenna W.J. A novel dominant mutation in plakoglobin causes arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet. 2007; 81: 964-973 Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar ] so ARVC is considered a disease of the desmosome. Desmin mutations as a cause of right ventricular heart failure affect the intercalated disksHeart RhythmVol. 7Issue 8PreviewMutations in the gene encoding desmin (DES), an intermediate filament protein, underlie a heterogeneous phenotype, which is referred to as desmin-related myopathy (DRM). Right ventricular involvement including an arrhythmogenic right ventricular cardiomyopathy (ARVC)(-like) phenotype has occasionally been described in DES mutation-carrying patients. Full-Text PDF