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。 公共卫生相关性：癫痫是人类最常见的神经疾病之一，影响多达3%的人口。虽然很明显癫痫有很强的遗传成分，但已知的基因仍然很少。Epi4K项目将确定癫痫的新基因和遗传途径，并将通过改进诊断、预后和复发风险信息直接使癫痫患者及其家人受益。更好地了解与大脑正常发育和功能有关的基因。 免责声明：请注意，以下批评是由评审员在研究小组会议之前准备的，基本上是以未经编辑的形式提供的。虽然审查员有机会根据小组的讨论更新或修订其书面评价，但不能保证在会议讨论之后更新了个别批评意见。因此，这些评论可能不能完全反映评审员在小组讨论结束时的最终意见或小组的最终多数意见。因此，讨论纪要和总结是审查员在会议上实际上认为至关重要的最后结论。

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. PUBLIC HEALTH RELEVANCE: Epilepsy is one of the most common neurological disorders in humans, affecting up to 3% of the population. Although it is clear that there is a strong genetic component for epilepsy, there are still only a few genes known. The Epi4K project will identify new genes and genetic pathways in epilepsy and will directly benefit individuals with epilepsy and their families through improved diagnostic, prognostic and recurrence risk information. Greater understanding of the genes involved in normal development and function of the brain. Disclaimer: Please note that the following critiques were prepared by the reviewers prior to the Study Section meeting and are provided in an essentially unedited form. While there is opportunity for the reviewers to update or revise their written evaluation, based upon the group's discussion, there is no guarantee that individual critiques have been updated subsequent to the discussion at the meeting. Therefore, the critiques may not fully reflect the final opinions of th individual reviewers at the close of group discussion or the final majority opinion of the group. Thus the Resume and Summary of Discussion is the final word on what the reviewers actually considered critical at the meeting.