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Review
. 2018 Aug;10(4):973-982.
doi: 10.1007/s12551-018-0437-0. Epub 2018 Jul 11.

Genetics of and pathogenic mechanisms in arrhythmogenic right ventricular cardiomyopathy

Anita Kiran Vimalanathan  1 , Elisabeth Ehler  1   2 , Katja Gehmlich  3
Affiliations
Review

Genetics of and pathogenic mechanisms in arrhythmogenic right ventricular cardiomyopathy

Anita Kiran Vimalanathan et al. Biophys Rev. 2018 Aug.

Abstract

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart disease, associated with a high risk of sudden cardiac death. ARVC has been termed a 'disease of the desmosome' based on the fact that in many cases, it is caused by mutations in genes encoding desmosomal proteins at the specialised intercellular junctions between cardiomyocytes, the intercalated discs. Desmosomes maintain the structural integrity of the ventricular myocardium and are also implicated in signal transduction pathways. Mutated desmosomal proteins are thought to cause detachment of cardiac myocytes by the loss of cellular adhesions and also affect signalling pathways, leading to cell death and substitution by fibrofatty adipocytic tissue. However, mutations in desmosomal proteins are not the sole cause for ARVC as mutations in non-desmosomal genes were also implicated in its pathogenesis. This review will consider the pathology, genetic basis and mechanisms of pathogenesis for ARVC.

Keywords: Arrhythmogenic right ventricular cardiomyopathy; Desmocollin; Desmoglein; Desmoplakin; Desmosomes; Plakoglobin; Plakophilin; Sudden cardiac death.

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Conflict of interest statement

Anita Kiran Vimalanathan declares that she has no conflict of interest. Elisabeth Ehler declares that she has no conflict of interest. Katja Gehmlich declares that she has no conflict of interest.

This article does not contain any studies with human participants or animals performed by any of the authors.

Figures

Fig. 1
Fig. 1
Schematic drawing of a desmosome: Intercellular connections between two cardiomyocytes (only partially shown) are mediated by the transmembrane proteins, the desmosomal cadherins desmocollin 2 (Dsc2) and desmoglein 2 (Dsg2). The link to the cytoskeleton, the intermediate filaments composed of desmin, is mediated by a complex consisting of desmoplakin, plakoglobin and plakophilin-2. Dsc2 also interacts with the gap junction protein connexin-43. PM stands for plasma membrane
See this image and copyright information in PMC

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