Proost Virginnio M, van den Berg Maarten P, Remme Carol Ann, Wilde Arthur A M
Department of Clinical Cardiology, Heart Centre, Amsterdam Cardiovascular Sciences, Heart Failure & Arrhythmias, Amsterdam University Medical Centres, location Academic Medical Centre/University of Amsterdam, Amsterdam, The Netherlands.
Department of Cardiology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
Neth Heart J. 2023 Aug;31(7-8):263-271. doi: 10.1007/s12471-023-01799-8. Epub 2023 Jul 20.
The SCN5A-1795insD founder variant is a unique SCN5A gene variant found in a large Dutch pedigree that first came to attention in the late 1950s. To date, this is still one of the largest and best described SCN5A founder families worldwide. It was the first time that a single pathogenic variant in SCN5A proved to be sufficient to cause a sodium channel overlap syndrome. Affected family members displayed features of Brugada syndrome, cardiac conduction disease and long QT syndrome type 3, thus encompassing features of both loss and gain of sodium channel function. This brief summary takes us past 70 years of clinical experience and over 2 decades of research. It is remarkable to what extent researchers and clinicians have managed to gain understanding of this complex phenotype in a relatively short time. Extensive clinical, genetic, electrophysiological and molecular studies have provided fundamental insights into SCN5A and the cardiac sodium channel Nav1.5.
SCN5A-1795insD始祖变异是在一个大型荷兰家系中发现的独特的SCN5A基因变异，该家系在20世纪50年代末首次受到关注。迄今为止，这仍然是全球最大且描述最详尽的SCN5A始祖家族之一。这是首次证明SCN5A中的单一致病变异足以导致钠通道重叠综合征。受影响的家庭成员表现出Brugada综合征、心脏传导疾病和3型长QT综合征的特征，因此涵盖了钠通道功能丧失和获得的特征。这一简短总结涵盖了70多年的临床经验和20多年的研究。研究人员和临床医生在相对较短的时间内对这种复杂表型的理解程度令人瞩目。广泛的临床、遗传、电生理和分子研究为SCN5A和心脏钠通道Nav1.5提供了基本见解。
