TGF 3 mutations cause arrhythmogenic right ventricular dysplasia type 1 and open the door to understanding the biological role of TGF 3 (where there's a will, there's a way): EXPERT'S PERSPECTIVE

Abstract

This editorial refers to an article by G. Beffagna et al . [10][1] published in Cardiovascular Research in 2005. It is accompanied by a retrospective editorial by one of the authors of that original article, A. Rampazzo (doi:10.1093/cvr/cvs221), as part of this Spotlight on Landmark Papers in Cardiovascular Research . Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited myocardial disease characterized by progressive fibrofatty replacement of the right ventricular myocardium, leading to right ventricular failure and arrhythmias.1,2 The left ventricle can also be involved, and in some patients, it can be the predominant site of involvement. The estimated prevalence of the disease in the general population ranges from 1:1000 to 1:5000.1,2 ARVC/D is a leading cause of sudden cardiac death (SCD), especially in young adults and athletes.1,2 The current diagnostic criteria are based on the presence of major and minor standardized criteria including ECG, ventricular arrhythmias, right ventricular function and morphology, histopathology, and family history.3 ARVC/D is a familial disease in at least 50% of cases, usually transmitted as an autosomal dominant trait, with reduced penetrance and highly variable clinical expression.1,2,4 ARVC/D has been associated with mutations in genes encoding cardiac desmosomal proteins involved in cell-to-cell interaction, including plakophilin-2 ( PKP2 ), desmoplakin ( DSP ), desmoglein-2 ( DSG2 ), desmocollin-2 ( DSC2 ), and plakoglobin ( JUP ).1–4 In addition, two complex cardiocutaneous disorders with autosomal recessive inheritance, the Naxos disease and the Carvajal syndrome, in which ARVC/D is associated with palmoplantar keratoderma and woolly hair, are also associated with homozygous mutations in JUP and in DSP , respectively. These findings confirmed that desmosomal dysfunction might be the final common pathway in the pathogenesis of ARVC/D. Desmosomes are protein complexes in the intercalated disk that are responsible for mechanical coupling of cardiac myocytes. … [1]: #ref-10