兰尼碱受体2新生基因突变R2401H致反复晕厥相关儿茶酚胺敏感性室性心动过速

Recurrent syncope related to catecholaminergic polymorphic ventricular tachycardia due to de novo RyR2-R2401H mutation

目的探讨1例儿茶酚胺敏感性室性心动过速（CPVT）患者临床和分子遗传学特征。 方法对2013年3月南昌大学第二附属医院心内科所收集1例CPVT患者的静息心电图、超声心动图和运动平板试验等临床资料进行分析，并采集患者及其相关家族成员和400例同族健康人外周静脉血样标本，使用DNA直接测序法对6个CPVT致病相关候选基因兰尼碱受体2（RyR2）、集钙蛋白（CASQ2）、TRDN、CALM1、KCNJ2及ANKB的外显子，以及外显子与内含子交界区序列进行直接测序，以筛查CPVT相关基因变异，分析基因型与表现型关系，并指导临床治疗。 结果收集到CPVT患者1例，因运动或受惊吓后出现反复晕厥，无晕厥及猝死家族史，静息心电图及超声心动图结果正常，运动平板试验可诱发双向和多形性室性心动过速。遗传检测发现该患者携带CPVT致病基因突变RyR2－R2401H，其父母、姐姐及400例对照中均未携带此突变，余5个候选基因未见突变。患者经高剂量琥珀酸美托洛尔（118.75 mg/d）治疗有效，随访2年无晕厥发作。 结论首次报道中国人CPVT相关RyR2－R2401H突变，高剂量美托洛尔可有效治疗RyR2基因突变所致CPVT。

ObjectiveTo explore the clinical and molecular genetic features of a Chinese patient with catecholaminergic polymorphic ventricular tachycardia （CPVT）. MethodsClinical data including resting electrocardiography, echocardiography and treadmill exercise testing of a patient with CPVT admitted to our department in March 2013 were analyzed, and the peripheral venous blood samples of the patient and his family members and 400 ethnicity-matched healthy controls were obtained. All exons and exon-intron boundaries of the six CPVT-related genes including RYR2, CASQ2, TRDN, CALM1, KCNJ2 and ANKB were sequenced to detect the variants related to CPVT. The relationship between the genotypes and phenotypes was analyzed to direct the target therapy. ResultsRecurrent syncope induced either by exercise or extreme frightened fear was observed in this patient. There was no positive family history of syncope or sudden death. The resting electrocardiography and echocardiography of the patient were normal, while the exercise testing revealed bidirectional and polymorphic ventricular tachycardia. A cardiac ryanodine receptor gene mutation （R2401H） was identified in this patient, while this mutation was absent in his parents and sister and 400 controls. No variant was detected in the remaining five candidate genes. Treatment with high dose of metoprolol succinate （118.75 mg/d） was effective and patient was free of syncopal attack during the 2 years follow-up. ConclusionThis is the first report on RyR2-R2401H mutation in Chinese patient with CPVT, and high dose of metoptolol is the effective therapy option for CPVT related to RyR2 mutation.