癫痫是神经科常见病，患者死亡风险显著增高。SUDEP是癫痫患者早逝的重要原因。SUDEP的发生与先天遗传易感性有关。前期研究表明SCN5A基因突变是部分癫痫患者发生SUDEP的重要易感基因。SCN5A突变与多种可致恶性心律失常的心脏疾病有关，引起猝死的易感性。既往报道脑内边缘区(海马等)均存在SCN5A表达，但脑内SCN5A具体功能是什么？SCN5A基因突变是否是癫痫猝死的高危因素？这些问题仍没有答案。本课题提出假设：SCN5A基因突变除了可引起心律失常导致个体获得猝死的易感性外，还可引起神经元电生理异常，从而使个体获得癫痫的易感性，故SCN5A基因突变可使个体出现癫痫与猝死的双重表型，从而导致SUDEP的发生。拟通过建立SCN5A突变大鼠模型，在体研究该大鼠癫痫发作阈值、围发作期猝死率，离体研究该大鼠神经元电生理特征、痫样放电频率以及可能的分子生物学机制，从全新角度探索SUDEP发生机制

Epilepsy was a common disease in the neurology department and the mortality was higher among people with epilepsy (PWE). SUDEP was the main reason of premature death among PWE. It was widely accepted that SUDEP was relevent to genetic susceptibility. Variants in SCN5A were important origin of genetic susceptibility of SUDEP in some PWE. Some variants in SCN5A was related to heart diseases which could result in fatal arrythmia and lead to susceptibility to sudden death according to previous reports. And there were SCN5A transcripts in limbic region (hippocampus) in brain. However, the function of SCN5A in the brain was unclear. Was mutation in SCN5A a risk factor of SUDEP？ There was still no answer for this question. We rose the hypothesis that mutation in SCN5A could result in abnormalities in the electrophysiology of neuron and cause predisposition for seizures, besides causing fatal arrythmia which could lead to susceptibility to sudden death. Therefore, patients with mutation in SCN5A could have the phenotype of epilepsy and sudden death, which could cause SUDEP. In this study, we planned to establish SCN5A-mutant rats, investigating the threshold of seizure, sudden death rate in peri-ictal period in vitro, and electrophysiological characteristics, frequency of epileptiform discharge, probable biomolecular mechanism in vivo. Thus, we try to investigate the mechanism of SUDEP from a new view.