Aizawa Yoshiyasu, Ueda Kazuo, Komura Satoru, Washizuka Takashi, Chinushi Masaomi, Inagaki Natsuko, Matsumoto Yuji, Hayashi Takeharu, Takahashi Megumi, Nakano Noritsugu, Yasunami Michio, Kimura Akinori, Hiraoka Masayasu, Aizawa Yoshifusa
Int J Cardiol. 2005 Mar 18;99(2):343-5. doi: 10.1016/j.ijcard.2003.11.050.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an autosomal dominant inherited disorder characterized by adrenergic induced polymorphic ventricular tachycardias and associated with sudden cardiac death. The human cardiac ryanodine receptor gene (RyR2) was linked to CPVT. A 20-year-old male was referred to our hospital because of recurrent syncope after physical and emotional stress. Routine cardiac examinations including catheterization revealed no structural abnormality. Exercise on treadmill induced premature ventricular contraction in bigeminy and bidirectional ventricular tachycardia was induced during isoproterenol infusion. Beta-blocking drug was effective in suppressing the arrhythmias. We performed genetic screening by PCR-SSCP method followed by DNA sequencing, and a novel missense mutation R2401H in RyR2 located in FKBP12.6 binding region was identified. This mutation was not detected in 190 healthy controls. Since FKBP12.6 plays a critical role in Ca channel gating, the R2401H mutation can be expected to alter Ca-induced Ca release and E-C coupling resulting in CPVT. This is the first report of RyR2 mutation in CPVT patient from Asia including Japan.
儿茶酚胺能性多形性室性心动过速（CPVT）是一种常染色体显性遗传性疾病，其特征为肾上腺素能诱导的多形性室性心动过速，并与心源性猝死相关。人类心脏兰尼碱受体基因（RyR2）与CPVT有关。一名20岁男性因在身体和情绪应激后反复晕厥而被转诊至我院。包括心导管检查在内的常规心脏检查未发现结构异常。跑步机运动诱发室性早搏二联律，异丙肾上腺素输注期间诱发双向室性心动过速。β受体阻滞剂可有效抑制心律失常。我们采用PCR-SSCP方法进行基因筛查，随后进行DNA测序，在位于FKBP12.6结合区域的RyR2中鉴定出一个新的错义突变R2401H。在190名健康对照中未检测到该突变。由于FKBP12.6在钙通道门控中起关键作用，预计R2401H突变会改变钙诱导的钙释放和兴奋-收缩偶联，从而导致CPVT。这是包括日本在内的亚洲CPVT患者中首次关于RyR2突变的报道。
