新生儿惊厥是常见疾病，部分患儿原因不明，遗传因素可能是其重要致病机制。本课题组通过全外显子组测序，在一家系中发现携带CNTNAP2基因突变的惊厥新生儿，提示CNTNAP2基因是导致新生儿惊厥的候选基因。CNTNAP2基因涉及多种神经系统发育障碍，但在新生儿惊厥发生中的作用尚不明确。因此，本课题拟：1.在不明原因惊厥新生儿队列中，进行CNTNAP2基因型分析；2.将CNTNAP2基因突变患儿皮肤成纤维细胞诱导分化为多能干细胞后进一步分化为神经元，观察CNTNAP2基因突变神经细胞的形态及电生理特征，并观察CNTNAP2基因对神经细胞分化成熟及功能的影响及其调控机制；3.利用CRISPR/Cas9的方法，将突变回复为野生型，分析是否对神经系统功能产生回复作用；4.构建CNTNAP2基因突变斑马鱼模型，进行行为学观察和惊厥关关联机制研究，以期阐明CNTNAP2基因在新生儿惊厥中的作用及其机制。

Neonatal seizures are common diseases, which have complex causes. The causes in some newborns are unknown. Genetic factors may be important in neonatal seizures. In our previous study, we found a neonate with seizures carrying CNTNAP2 gene mutation, suggesting that CNTNAP2 gene is a candidate gene that responsible for neonatal seizures. Previous studies on the CNTNAP2 gene, confirmed that the genes involved in a variety of developmental disorders of the nervous system, but its role in neonatal seizures is unclear. Therefore, we will do the following things in this project: 1. Analyze the genotype of CNTNAP2 in unexplained seizures in newborns; 2. Get the fibroblasts from the patient with CNTNAP2 gene mutations, and induced the fibroblasts into pluripotent stem cells, and then further induced into neurons. Neuronal morphology and electrophysiological characteristics, and the role of CNTNAP2 gene in neuronal differentiation and maturation will be investigated; 3. Reverse the mutation into wild type by CRISPR/Cas9 method, and analyze whether the function of the nervous system is reversed or not; 4. Build zebrafish model with CNTNAP2 gene mutation, and observe the behavioral changes and investigate the associated mechanisms. Through these studies, we want to clarify the role and mechanism of CNTNAP2 gene in neonatal seizures.