Priori Silvia G, Napolitano Carlo, Memmi Mirella, Colombi Barbara, Drago Fabrizio, Gasparini Maurizio, DeSimone Luciano, Coltorti Fernando, Bloise Raffaella, Keegan Roberto, Cruz Filho Fernando E S, Vignati Gabriele, Benatar Abraham, DeLogu Angelica
Molecular Cardiology, IRCCS Fondazione S. Maugeri, University of Pavia, Pavia, Italy.
Circulation. 2002 Jul 2;106(1):69-74. doi: 10.1161/01.cir.0000020013.73106.d8.
Mutations in the cardiac ryanodine receptor gene (RyR2) underlie catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited arrhythmogenic disease occurring in the structurally intact heart. The proportion of patients with CPVT carrying RyR2 mutations is unknown, and the clinical features of RyR2-CPVT as compared with nongenotyped CPVT are undefined.
Patients with documented polymorphic ventricular arrhythmias occurring during physical or emotional stress with a normal heart entered the study. The clinical phenotype of the 30 probands and of 118 family members was evaluated, and mutation screening on the RyR2 gene was performed. Arrhythmias documented in probands were: 14 of 30 bidirectional ventricular tachycardia, 12 of 30 polymorphic ventricular tachycardia, and 4 of 30 catecholaminergic idiopathic ventricular fibrillation; RyR2 mutations were identified in 14 of 30 probands (36% bidirectional ventricular tachycardia, 58% polymorphic ventricular tachycardia, 50% catecholaminergic idiopathic ventricular fibrillation) and in 9 family members (4 silent gene carriers). Genotype-phenotype analysis showed that patients with RyR2 CPVT have events at a younger age than do patients with nongenotyped CPVT and that male sex is a risk factor for syncope in RyR2-CPVT (relative risk=4.2).
CPVT is a clinically and genetically heterogeneous disease manifesting beyond pediatric age with a spectrum of polymorphic arrhythmias. beta-Blockers reduce arrhythmias, but in 30% of patients an implantable defibrillator may be required. Genetic analysis identifies two groups of patients: Patients with nongenotyped CPVT are predominantly women and become symptomatic later in life; patients with RyR2 CPVT become symptomatic earlier, and men are at higher risk of cardiac events. These data provide a rationale for prompt evaluation and treatment of young men with RyR2 mutations.
心脏兰尼碱受体基因（RyR2）突变是儿茶酚胺能多形性室性心动过速（CPVT）的基础，CPVT是一种发生于结构正常心脏的遗传性致心律失常疾病。携带RyR2突变的CPVT患者比例尚不清楚，与未进行基因分型的CPVT相比，RyR2 - CPVT的临床特征也不明确。
在体力或情绪应激期间发生多形性室性心律失常且心脏正常的患者进入本研究。评估了30例先证者和118名家庭成员的临床表型，并对RyR2基因进行了突变筛查。先证者记录的心律失常包括：30例中有14例双向性室性心动过速、12例多形性室性心动过速和4例儿茶酚胺能特发性心室颤动；30例先证者中有14例（双向性室性心动过速占36%，多形性室性心动过速占58%，儿茶酚胺能特发性心室颤动占50%）以及9名家庭成员（4名沉默基因携带者）检测到RyR2突变。基因型 - 表型分析表明，与未进行基因分型的CPVT患者相比，RyR2 - CPVT患者发病年龄更小，并且男性是RyR2 - CPVT发生晕厥的危险因素（相对风险 = 4.2）。
CPVT是一种临床和遗传异质性疾病，在儿童期以后表现为一系列多形性心律失常。β受体阻滞剂可减少心律失常，但30%的患者可能需要植入式除颤器。基因分析确定了两组患者：未进行基因分型的CPVT患者以女性为主，发病较晚；RyR
