Identification of a novel gene involved in Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia
Year: 2012
Type: dissertation
Study design: Observational Study
Abstract: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a genetic cardiac disease inherited as an autosomal dominant trait with incomplete penetrance and variable expressivity. Its main feature is the progressive substitution of the myocardium with fatty or fibro-fatty tissue, involving predominantly the right ventricle. Clinically, ARVC/D is characterized by ventricular arrhythmias, often associated with syncope and sudden cardiac death, especially in the young and athletes. Up to now, several disease genes have been identified, including 5 encoding desmosomal proteins. In this study, mutation screening for desmosomal genes performed in 80 consecutive unrelated Italian probands failed to detect mutation in about half of index cases, thus suggesting further genetic heterogeneity. On the basis of alphaT-catenin (a protein of cardiac area composita) cellular localization and function, mutation screening was then performed in CTNNA3 candidate gene in 76 affected subjects, negative for mutations in desmosomal genes. Four mutations have been detected. In vitro functional studies assessed the pathogenicity for two of them. For the first time mutations in CTNNA3 have been detected in a human disease. Particularly, the recurrence of pathogenic mutations in CTNNA3 gene in ARVC/D patients expands the concept of this disease beyond desmosomes
Author: Martina Calore
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2285712916