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 创始人变体是在一个大型荷兰血统中发现的独特SCN5A基因变体，于 20 世纪 50 年代末首次引起人们的注意。迄今为止，这仍然是全球最大、描述最清楚的SCN5A创始人家族之一。这是首次证明SCN5A中的单一致病性变异足以引起钠通道重叠综合征。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，因此包含钠通道功能丧失和增强的特征。这个简短的总结涵盖了我们过去 70 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成功地了解了这种复杂的表型，这一点是值得注意的。广泛的临床、遗传学、电生理学和分子研究为SCN5A和心脏钠通道 Nav1.5提供了基本见解。