4 of 7: Epi4K: Epileptic Encephalopathies Project

描述(申请人提供)：无墙Epi4K中心的主要目标是增加对人类癫痫遗传基础的了解，以改善患有这些疾病的患者和家庭成员的福祉。这种改善将以更好的诊断、治疗和治愈的形式出现。为了实现这一目标，Epi4K旨在分析来自几个主要研究小组的研究人员收集的大量表型良好的癫痫患者和家系的外显子和基因组。这个项目的具体目标(7个中的4个：癫痫脑病)是通过从500名患有两种严重儿童癫痫脑病的患者的外显子组中挖掘序列数据来发现基因突变或缺失。婴儿痉挛(IS)和Lennox Gastaut综合征(LGS)，以了解这些突变如何适应大脑内更广泛的发育互动网络，并将这些已定义的癫痫的原因与其他儿童期癫痫脑病(EE)进行比较。加州大学旧金山分校的Sherr博士、墨尔本大学的Scheffer博士和华盛顿大学的Mford博士将共同指导这一项目。在Epi4K队列中发现导致IS/LGS和其他严重儿童EE的新基因将加深我们对癫痫遗传学的理解，并导致对癫痫病理生理学的更好理解，以及为诊断和治疗提供更好的工具的可能性。

DESCRIPTION (provided by applicant): The primary goal of the Epi4K Center Without Walls is to increase understanding of the genetic basis of human epilepsy in order to improve the well-being of patients and family members living with these disorders. This improvement will come in the form of better diagnostics, treatments and cures. To accomplish this goal, Epi4K aims to analyze the exomes and genomes of a large number of well-phenotyped epilepsy patients and families collected by investigators from several major research groups. The specific goals of this project (4 of 7: Epileptic Encephalopathies) are to discover mutations or deletions in genes by mining sequence data from exomes of 500 patients with two severe childhood epileptic encephalopathies. Infantile Spasms (IS) and Lennox Gastaut Syndrome (LGS), to understand how these mutations fit into a broader network of developmental interactions within the brain and to compare the causes of these defined epilepsies with other epileptic encephalopathies (EE) of childhood. Dr. Sherr from UCSF, Dr. Scheffer from the University of Melbourne and Dr. Mefford from the University of Washington will co-direct this project. The discovery of novel genes that lead to IS/LGS and other severe childhood EE in the Epi4K cohorts will further our understanding of epilepsy genetics and lead to a better understanding of epilepsy pathophysiology and to the possibility of better tools for diagnosis and treatment.