Wilde Arthur A M, van den Berg Maarten P
Department of Clinical and Experimental Cardiology, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands.
J Electrocardiol. 2005 Oct;38(4 Suppl):145-9. doi: 10.1016/j.jelectrocard.2005.06.103.
In the last 10 years the molecular substrate of a diversity of primary electrical diseases has been unraveled. Disease-causing mutations in ion-channel genes have been identified and have challenged clinical and basic electrophysiologists to mechanistically link the observed genetic aberrancies to the phenotype. Indeed, in collaborative efforts of clinical cardiologists, clinical and molecular geneticists, basic electrophysiologists and computer modellers, the pathophysiology of many clinical electrocardiographic findings have been elucidated in detail. The family described concerns an 8-generation SCN5a-linked family with a high incidence of nocturnal sudden death. The phenotype is characterised by bradycardia-dependent QT-prolongation, right precordial ST-elevation, conduction disease at all cardiac compartments, and sinus node disfunction. Heterologous expression of the mutant sodium channels demonstrated altered channel characteristics which, introduced in elegant computer modeling studies, nicely explained the complex phenotype. As such these studies serve as a good example of what can be reached in a multidisciplinary approach with clinical and basic scientists.
在过去十年中，多种原发性电疾病的分子基础已被揭示。离子通道基因中的致病突变已被识别，这促使临床和基础电生理学家从机制上将观察到的基因异常与表型联系起来。事实上，在临床心脏病学家、临床和分子遗传学家、基础电生理学家以及计算机建模人员的共同努力下，许多临床心电图表现的病理生理学已得到详细阐明。所描述的这个家族是一个与SCN5a相关的八代家族，夜间猝死发生率很高。其表型特征为心动过缓依赖性QT延长、右胸前导联ST段抬高、所有心脏腔室的传导疾病以及窦房结功能障碍。突变钠通道的异源表达显示出通道特性的改变，在精密的计算机建模研究中引入这些改变后，很好地解释了这种复杂的表型。因此，这些研究是临床科学家和基础科学家采用多学科方法所能取得成果的一个很好范例。
