The primary arrhythmia syndromes:: Same mutation, different manifestations.: Are we starting to understand why?
The primary arrhythmia syndromes:: Same mutation, different manifestations.: Are we starting to understand why?
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DOI：
10.1111/j.1540-8167.2007.01073.x
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发表时间：
2008-04-01
影响因子：
2.7
通讯作者：
Bezzina, Connie R.
中科院分区：
文献类型：
--
作者：
Scicluna, Brendon P.;Wilde, Arthur W.;Bezzina, Connie R.
原发性心律失常综合征。主要在编码原发性心律失常综合征的心脏离子通道蛋白的基因中发现致病性突变，对这些疾病的治疗产生了显着影响，特别是对于长 QT 综合征患者。基因诊断测试的出现增加了一种重要的诊断工具，为患者管理提供了新的机会，例如早期（症状前）识别和治疗有致命性心律失常风险的患者、风险分层以及安装基因特异性治疗。然而，家庭内因果突变的鉴定允许独立于心电图特征和心律失常表现对其他家庭成员进行诊断，这一事实很快导致人们认识到，在单个离子通道基因携带相同突变的家庭成员中可能会观察到临床表现的广泛变异性（例如心电图异常和/或症状的程度）。人们普遍认为，这种临床变异源于环境和遗传修饰物与特定致病突变之间的相互作用。这篇分子视角文章回顾了心律失常综合征中疾病表达修饰因子的最新知识，特别是遗传修饰因子。
The Primary Arrhythmia Syndromes. The discovery of pathogenic mutations primarily in genes encoding cardiac ion-channel proteins underlying the primary cardiac arrhythmia syndromes has had a remarkable impact on the management of these disorders, especially in patients with the long-QT syndrome. The availability of a genetic diagnostic test has added an important diagnostic tool, providing new opportunities for patient management such as early (presymptomatic) identification and treatment of patients at risk of developing fatal arrhythmias, risk stratification, and installation of gene-specific therapy. However, the fact that the identification of the causal mutation within a family allows diagnosis in other family members independently from the ECG features and arrhythmic manifestations quickly led to the recognition that extensive variability in clinical manifestations (e.g., extent of ECG abnormality and/or symptomatology) may be observed among family members carrying an identical mutation in a single ion channel gene. It is commonly held that this clinical variability stems from interactions between environmental and genetic modifiers with the particular pathogenic mutation. This Molecular Perspectives article reviews current knowledge on these modifiers of disease expression in the cardiac arrhythmia syndromes with particular reference to genetic modifiers.