Novel mutations in arrhythmogenic right ventricular cardiomyopathy from Indian population

Abstract

BACKGROUND:Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive condition with right ventricular myocardium being replaced by fibro-fatty tissue. The spectrum of the expression may range from benign palpitations to the most malignant sudden death. Most of the mutations identified for the condition are localized in desmosomal proteins although three other nondesmosomal genes (cardiac ryanodine receptor-2, TGF-β3, and TMEM43) have also been implicated in ARVC. Both desmosomal and nondesmosomal genes were screened in a set of patients from local population.MATERIALS AND METHODS:A set of 34 patients from local population were included in this study. Diagnosis was based on the criteria proposed by task force of European Society of Cardiology/International Society and Federation of Cardiology. Polymerase chain reaction-based single-strand conformation polymorphism analysis was carried out, and samples with abnormal band pattern were commercially sequenced.RESULTS:Screening of cardiac ryanodine receptor revealed an insertion of a base in the intronic region of exon-28 in a patient, leading to a creation of a cryptic splice site. Screening of plakohilin-2 for mutations revealed an abnormal band pattern in three patients. Two of them had similar abnormal band pattern for exon-3.1. Sequencing revealed a novel 2 base pair deletion (433_434 delCT), which would lead to premature truncation of the protein (L145EfsX8). Another patient showed abnormal band pattern for exon-3.2 and sequencing revealed a missense mutation C792T leading to amino acid change P244L, in N-terminal, and this substitution may cause disturbances in the various protein–protein interactions.CONCLUSION:This study reports novel cardiac ryanodine receptor (RyR-2) mutations and Pkp-2 for the first time from Indian population.

The Electrocardiographic Manifestations of Arrhythmogenic Right Ventricular Dysplasia

“…With over 100 mutations identified in DCM, LMNA is also responsible for ARVD [ 27 ]. RYR2 , the cardiac ryanodine receptor gene mainly accounting for catecholaminergic polymorphic ventricular tachycardia, is linked to ARVD as well [ 28 , 29 ].…”

Mushroom-Shaped Right Ventricular Outflow Tract Aneurysm May Provide an Early Clue in Pediatric Arrhythmogenic Right Ventricular Cardiomyopathy

“…Genotype-phenotype correlation studies in adults have reported the PKP2 variant to be associated with a higher incidence of RV involvement, especially RVOT aneurysms. 10 We speculate that the presence of PKP2 variant in children may be associated with the formation of an ms-RVOT. Due to a limited number of patients, we can merely point out this association but cannot comment on any causal role of this genetic variant.…”

Comprehensive analysis of desmosomal gene mutations in Han Chinese patients with arrhythmogenic right ventricular cardiomyopathy

“…In addition, Dalal et al identified the same mutation in two female ARVC patients of North American Caucasian origin, but gave no further information regarding haplotype analysis [den Haan et al, 2009;Dalal et al, 2006a]. This same mutation was not identified in Japanese groups or an Indian group [Nakajima et al, 2012;Ohno et al, 2013;Pamuru et al, 2011]. van der Zwaag et al (2010) reported that this same mutation is a founder mutation in the Netherlands.…”