Pamuru Pranathi Rao, Maithili D V N, Mohiuddin Khalid, Calambur Narasimhan, Nallari Pratibha
Department of Genetics, Osmania University, Hyderabad, Andhra Pradesh, India.
Indian J Hum Genet. 2011 May;17(2):70-6. doi: 10.4103/0971-6866.86182.
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.
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.
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.
This study reports novel cardiac ryanodine receptor (RyR-2) mutations and Pkp-2 for the first time from Indian population.
致心律失常性右室心肌病（ARVC）是一种进行性疾病，右室心肌被纤维脂肪组织替代。其临床表现范围从良性心悸到最恶性的猝死。尽管另外三个非桥粒基因（心肌兰尼碱受体-2、转化生长因子-β3和跨膜蛋白43）也与ARVC有关，但已确定的该疾病的大多数突变位于桥粒蛋白中。对一组当地人群患者的桥粒和非桥粒基因进行了筛查。
本研究纳入了一组34名当地人群患者。诊断基于欧洲心脏病学会/国际心脏病学会和联合会工作组提出的标准。进行了基于聚合酶链反应的单链构象多态性分析，对条带模式异常的样本进行商业测序。
对心肌兰尼碱受体的筛查发现一名患者外显子28内含子区域插入了一个碱基，导致产生一个隐蔽剪接位点。对桥粒斑蛋白-2进行突变筛查时，三名患者出现条带模式异常。其中两名患者外显子3.1的条带模式相似。测序发现一个新的2个碱基对缺失（433_434 delCT），这将导致蛋白质过早截断（L145EfsX8）。另一名患者外显子3.2条带模式异常，测序发现一个错义突变C792T，导致N端氨基酸改变P244L，这种替代可能会干扰各种蛋白质-蛋白质相互作用。
本研究首次报道了来自印度人群的新型心肌兰尼碱受体（RyR-2）突变和桥粒斑蛋白-2（Pkp-2）突变。
