早期癫痫性脑病（EEEs）是新生儿和婴儿期症状最重、预后最差的癫痫表型。排除获得性脑损伤、遗传代谢病等已知原因后，仍有半数患儿病因不明。研究证实，基因突变及拷贝数变异与此部分EEEs密切相关。但由于EEEs涉及基因数量庞大、遗传异质性强，基于临床表型用一代测序技术检测费时，费用昂贵，特别是对罕见致病基因的检出率更低，导致了目前EEEs的诊疗面临巨大的困难。本研究基于高通量二代测序平台，利用目标序列捕获测序技术自主研制 "早期癫痫性脑病基因诊断芯片"，结合全基因组拷贝数变异分析方法，对不明原因的EEEs进行已知基因的高通量检测，建立从临床诊断到基因诊断、产前诊断的EEEs诊疗技术规范；在此基础上，寻找新的易感/致病基因，并进行群体分析和功能验证。对于这一问题的深入研究，将为EEEs的早期临床干预提供重要思路。其研究成果可望解决不明原因EEEs的诊断瓶颈问题，并提供候选基因进一步阐明其发病机制

Early epileptic encephalopathies (EEEs) are one of the epilepsy phenotypes in neonates and infants with the most severe symptoms and worst prognosis. Exclusion of acquired brain injury, genetic and metabolic diseases and other causes, there are still half of the EEEs with unknown etiology. To date, a few studies indicated that gene mutation and copy number variations (CNVs) are closely related with EEEs. However, detection technology based on sanger sequencing is time consuming, expensive and low detection rate especially for rare pathogenic gene because of the huge number of EEEs genes as well as their genetic heterogeneity and clinical phenotype, So, the diagnosis and treatment of EEEs is facing enormous difficulties. "Gene diagnosis chip of early-onset epileptic encephalopathies" was independently exploited based on target genomic DNA capturing system and next generation sequencing, which combined with CNVs, to do population screening for all EEEs patiets with unkown etiology, aiming to build a technical manual from clinical diagnosis to gene diagnosis and prenatal diagnosis. Furthermore, candidate susceptibility/pathogenic genes of EEEs are beening screened out through group analysis and functional studies. The research findings are expected to improve our understanding of early diagnosis and treatment of the EEEs, and to provide candidate genes to further clarify the pathogenesis, which propably solve the diagnosis bottleneck problem of unknown cause EEEs.