Arrhythmogenic cardiomyopathy (AC) is one of the most common inherited cardiomyopathies, characterized by progressive fibro-fatty replacement in the myocardium. Clinically, AC manifests itself with ventricular arrhythmias, syncope, and sudden death and shows wide inter- and intra-familial variability. Among the causative genes identified so far, those encoding for the desmosomal proteins plakophilin-2 (PKP2), desmoplakin (DSP), and desmoglein-2 (DSG2) are the most commonly mutated. So far, little is known about the molecular mechanism(s) behind such a varied spectrum of phenotypes, although it has been shown that the causative mutations not only lead to structural abnormalities but also affect the miRNA profiling of cardiac tissue. In this study, Martina Calore and collaborators studied the pathogenic effects of a nonsense mutation of the desmoglein-2 gene, both at the structural level and in terms of miRNA expression pattern.
For more information, see:
Calore M, Lorenzon A, Vitiello L, Poloni G, Khan MAF, Beffagna G, Dazzo E, Sacchetto C, Polishchuk R, Sabatelli P, Doliana R, Carnevale D, Lembo G, Bonaldo P, De Windt L, Braghetta P, Rampazzo A. A novel murine model for arrhythmogenic cardiomyopathy points to a pathogenic role of Wnt signalling and miRNA dysregulation. Cardiovasc Res. 2019;115:739-751. [https://doi.org/10.1093/cvr/cvy253 [PubMed] [PDF]
