Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN, USA.
Transl Res. 2013 Jan;161(1):1-14. doi: 10.1016/j.trsl.2012.08.005. Epub 2012 Sep 17.
Mutations in genes encoding ion channel pore-forming α-subunits and accessory β-subunits as well as intracellular calcium-handling proteins that collectively maintain the electromechanical function of the human heart serve as the underlying pathogenic substrate for a spectrum of sudden cardiac death (SCD)-predisposing heritable cardiac arrhythmia syndromes, including long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome (BrS), and catecholaminergic polymorphic ventricular tachycardia (CPVT). Similar to many Mendelian disorders, the cardiac "channelopathies" exhibit incomplete penetrance, variable expressivity, and phenotypic overlap, whereby genotype-positive individuals within the same genetic lineage assume vastly different clinical courses as objectively assessed by phenotypic features such electrocardiographic abnormalities and number/type of cardiac events. In this Review, we summarize the current understanding of the global architecture of complex electrocardiographic traits such as the QT interval, focusing on the role of common genetic variants in the modulation of ECG parameters in health and the environmental and genetic determinants of incomplete penetrance and variable expressivity in the heritable cardiac arrhythmia syndromes most likely to be encountered in clinical practice.
编码离子通道孔形成α亚基和辅助β亚基以及细胞内钙处理蛋白的基因突变，共同维持着人类心脏的机电功能，这些突变是一系列易导致心源性猝死（SCD）的遗传性心律失常综合征的潜在致病基础，包括长 QT 综合征（LQTS）、短 QT 综合征（SQTS）、Brugada 综合征（BrS）和儿茶酚胺能多形性室性心动过速（CPVT）。与许多孟德尔疾病一样，心脏“通道病”表现出不完全外显率、可变表达性和表型重叠，即在同一遗传谱系中基因型阳性的个体，根据心电图异常和心脏事件的数量/类型等表型特征进行客观评估，其临床表现差异很大。在这篇综述中，我们总结了目前对复杂心电图特征（如 QT 间期）的全球结构的理解，重点介绍了常见遗传变异在调节心电图参数方面的作用，以及在遗传性心律失常综合征中不完全外显率和可变表达性的环境和遗传决定因素，这些综合征在临床实践中最有可能遇到。
