Department of Cardiovascular Medicine, Nippon Medical School.
Circ J. 2013;77(12):2867-72. doi: 10.1253/circj.cj-13-1217. Epub 2013 Nov 7.
Over the past 2 decades, a number of inherited cardiac arrhythmias, including congenital long QT syndrome (LQTS) and Brugada syndrome (BrS), have been shown to have a link to mutations in genes encoding for ion channels or other membrane components. The recent HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited arrhythmia syndromes has updated the clinical diagnosis of congenital LQTS and BrS. Genetic studies have identified 13 forms of congenital LQTS in 50-80% of clinically affected patients. Genotype-phenotype correlations have been investigated in the 3 major genotypes, LQT1, LQT2 and LQT3 syndromes, resulting in genotype-specific management and therapy. More detailed analyses of each genotype have suggested mutation location-, type-, or function-specific differences in clinical phenotype among the LQT1, LQT2, and possibly LQT3 genotypes. In BrS, only one-third of affected patients can be genotyped, mainly in the sodium channel gene, SCN5A; therefore, clinical studies of genotype-phenotype relationships have been limited. More recently, a genome-wide association study using a gene array explored the role of common genetic variants (polymorphisms) as the susceptible or modifier gene in both congenital LQTS and BrS.
在过去的 20 年中，许多遗传性心律失常，包括先天性长 QT 综合征（LQTS）和 Brugada 综合征（BrS），已被证明与编码离子通道或其他膜成分的基因突变有关。最近的 HRS/EHRA/APHRS 专家共识声明对遗传性心律失常综合征患者的诊断和管理进行了更新，包括先天性 LQTS 和 BrS 的临床诊断。遗传研究已经在 50-80%的临床受影响患者中确定了 13 种先天性 LQTS 形式。在 3 种主要基因型（LQT1、LQT2 和 LQT3 综合征）中已经研究了基因型-表型相关性，导致了特定基因型的管理和治疗。对每个基因型的更详细分析表明，在 LQT1、LQT2 和可能的 LQT3 基因型中，临床表型存在突变位置、类型或功能特异性差异。在 BrS 中，只有三分之一的受影响患者可以进行基因分型，主要是在钠离子通道基因 SCN5A 中；因此，基因型-表型关系的临床研究受到限制。最近，一项使用基因芯片的全基因组关联研究探讨了常见遗传变异（多态性）作为先天性 LQTS 和 BrS 易感或修饰基因的作用。
