PRRT2相关性疾病（PRRT2-related Disorders，PRD）是一大类由于PRRT2基因突变所致疾病的总称，具有高度的临床异质性，包括了发作性动作诱发性运动障碍、良性家族性婴儿惊厥、高热惊厥、偏头痛、偏瘫型偏头痛等许多类型，但其发病机制尚未明确。综合PRD的临床发作特点，膜稳定剂卡马西平治疗有效，多巴胺受体拮抗剂氟哌啶醇加重症状，PRRT2相互作用蛋白SNAP25与突触囊泡神经递质的释放密切相关等因素，推测PRRT2相关疾病可能与神经递质释放障碍有关。利用前期工作中已经完成的PRRT2条件敲除小鼠，人皮肤成纤维细胞诱导的iPS细胞等，本课题将采用免疫组化和免疫荧光、高效液相色谱分析、脑深部碳纤电极活体记录、神经递质释放试验等方法以期明确神经递质释放在PRRT2相关疾病致病机制中的作用，为进一步阐明PRD的机制打下基础。

PRRT2-related disorder（PRD） is a group of heterogeneous diseases caused by PRRT2 mutations, including parosysmal kinesigenic dyskinesia, benign familial infantile convulsions, hyperpyretic convulsion, migraine and hemiplegic migraine. But the mechanism of these disorders remains unclear. We speculate that the dysfunction of neurotransmitter release may be associated with the pathogenesis of PRD for its clinical features, effective response to membrane stabilizer carbamazepine, manifestation aggravated by dopamine receptor antagonist haloperidol, and the finding that PRRT2 interacted protein SNAP25 is related with the synaptic vesicles neurotransmitters release. On the basis of the preliminary work in which PRRT2 conditional knock-out mice and iPS cells induced from human dermal fibroblasts are accomplished, in this project, we will apply immunohistochemistry, immunofluorescence, HPLC analysis and carbon fiber electrode deep brain neurotransmitter release test to clarify the role of neurotransmitter release in the pathogenesis of PRRT2-related diseases.