Regulatory mutations in transforming growth factor-?3 gene cause arrhythmogenic right ventricular cardiomyopathy type 1

Abstract

We identified TGFbeta3 as the disease gene involved in ARVD1. The identification of a novel ARVC gene will increase the power of the genetic screening for early diagnosis of asymptomatic carriers among relatives of ARVC patients.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a not so rare “disease of the desmosome” with multiple clinical presentations

“…Since mutations in desmosomal proteins such as PKP2, JUP, and DSP (Table 2) seem to be important in the pathogenesis of ARVC/D, the disease has been named "a disease of the desmosome" 30 . It is of interest that mutations in the regulatory domain of the transforming growth factor-β3 gene were identified recently in patients with ARVC/D 1 31 . TGF-β3 may play a role in desmosomal protein modulation.…”

Myocardial expression profiles of candidate molecules in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia compared to those with dilated cardiomyopathy and healthy controls

“…12 TGFB3, a cytokine involved in the modulation of desmosomal proteins and stimulation of fibrosis has also been reported to have an influence on the pathogenesis of myocardial fibrosis. 13 Experimental and clinical data suggest that other non-junctional cellular structures like the voltage-gated sodium channel (Nav 1.5), the sarcolemmal calcium channel regulating molecule PLN, and structural molecules are linked to desmosomes. 14 Especially PLN phosphorylation has been reported to play a key role in the pathophysiology of heart failure.…”

Arrhythmogenic right ventricular cardiomyopathy: asymptomatic to life threatening as illustrated by the cases of two sisters

“…Several genetic loci have been reported to be associated with the disease and mutations in six genes have been identified: ryanodine receptor, plakoglobin, desmoplakin and recently transforming growth factor-β, plakophilin-2 and desmoglein. [9][10][11][12][13][14][15][16] Patients with mutations in the ryanodine receptor gene, also called ARVC2, are more prone to develop arrhythmias. 17 The recognition that ARVC is frequently familial and can cause arrhythmic death leads to the challenge to identify family members who are at risk.…”