早发性癫痫性脑病（EOEE）是一组常见的癫痫综合征且预后不良，遗传因素被认为是EOEE发生的主要病因。前期研究中，我们通过全外显子组测序发现两个典型的EOEE患者各携带了一个位于CDK19的新发突变，分别为c.586A>G (p.Thr196Ala)、c.94T>C(p.Tyr32His)，并已成功构建了CDK19基因敲除SH-SY5Y细胞系、RNAi Cdk19敲低大鼠神经干细胞、CDK19突变患者的iPS细胞系、Cdk8（果蝇CDK19同源基因）基因编辑果蝇模型，同时观察到CDK19基因敲除SH-SY5Y细胞系、Cdk19 敲低大鼠神经干细胞增殖分化出现异常。本课题拟在前期研究基础上，基于SH-SY5Y细胞系、iPS细胞转化神经元及果蝇模型，应用基因编辑、转录组测序等分子生物学技术，探索新候选基因CDK19致EOEE发病的机制，为其精准治疗提供实验依据。

Early onset epilepsy encephalopathy (EOEE) is a group of common epilepsy syndrome with poor prognosis. Genetic factors are considered to be the main cause of EOEE. In the previous research, we found two De novo CDK19 mutations in two typical EOEE patients by whole exome sequencing，which are c.586A>G (p.Thr196Ala)、c.94T>C (p.Tyr32His) respectively . And we have successfully constructed gene-edited SH-SY5Y cell line,RNAi-mediated Cdk19 Knock-down rat neural stem cell line，CDK19 pathogenic mutation iPS cells and the Cdk8 (Drosophila CDK19 homologous gene) gene-edited drosophila model. Based on the previous research, this project intends to clarify the the relationship between CDK19 gene mutation and EOEE, and to elucidate the role of CDK19 and its regulatory pathway abnormalities in the development of EOEE. It will provide a laboratory basis for the precision treatment of EOEE.