Molecular medicine of inherited arrhythmias

编码心脏离子通道的各种基因突变会延迟心室的复极，从而导致长QT综合征(LQTS)。LQTS分为先天性和后天性两种类型。后者易患药物、电解质异常、心脏病、中枢神经疾病和代谢紊乱。先天性LQTS包括Romano-Ward综合征(RWS)和Jervell-Lange-Nielsen综合征(JLNS)。RWS具有常染色体显性遗传特征。相反，JLNS表现出常染色体隐性遗传特征，通常与先天性耳聋有关。到目前为止，至少发现了5个与LQTS相关的基因：KCNQ1、KCNH2、SCN5A、KCNE1和KCNE2，从而使我们能够进行基因筛查和基因特异性治疗。最近，另一例常染色体显性遗传性先天性LQTS被报道伴有周期性瘫痪和畸形特征(Andersen综合征)。编码心脏内向整流钾通道(Kir2.1)的KCNJ2有9个新的突变与该综合征有关。我们对这些编码离子通道及其相关蛋白的基因进行了广泛的遗传分析，并确定了疾病特有的遗传变异。此外，我们还进行了电生理测试，以证实基因突变是否会导致真正的功能变化。这些数据已作为上文所列原创论文发表。

Various mutations of genes coding cardiac ion channels delay the repolarization of the ventricle, thereby causing long QT syndrome (LQTS). LQTS has been classified as congenital and acquired forms. The latter is predisposed by drug, electrolyte abnormality, heart disease, central nerve disease, and metabolic disorder. Congenital LQTS consists of Romano-Ward syndrome (RWS) and Jervell-Lange-Nielsen syndrome (JLNS). The RWS shows autosomal dominant hereditary trait. In contrast, the JLNS shows autosomal recessive trait and is usually associated with congenital deafness. At least five responsible LQTS-related genes are identified to date: KCNQ 1, KCNH2, SCN5A, KCNE1, and KCNE2, thereby allowing us to make a genetic screening and a gene-specific therapy. More recently, another autosomal dominant congenital LQTS has been reported to accompany with periodic paralysis and dysmorphic features (Andersen's syndrome). Nine novel mutations in KCNJ2, coding cardiac inward rectifier potassium channels (Kir2.1), were found to relate with the syndrome. We have conducted extensive genetic analyses on these genes coding ion channels and their associated proteins and identified the disease specific genetic variants. Moreover, we had performed electrophysiological assay to confirm whether the genetic mutations induce the real functional change. Those data have been published as original papers as listed above.