Genetics of the rare epilepsy syndromes

癫痫是一种常见的神经疾病，具有很强的遗传影响。因此，了解癫痫障碍的遗传基础将为潜在的病理生理学提供新的见解，并导致新的诊断和治疗途径。这一合作研究项目将专注于罕见的癫痫综合征，这是一组家族性癫痫和癫痫性脑病的总称，其中许多代表严重的和治疗抵抗的癫痫。因此，特别是在RES中，迫切需要新的治疗策略。就遗传风险因素而言，RE通常代表极端的表型。遗传风险因素特别丰富，可能在更常见的癫痫中引领基因鉴定的道路。这个合作研究项目(CRP)旨在利用跨国大规模方法破译许多RES的遗传基础，汇集了能够接触到大量患者队列的癫痫专家和在基因定位和基因鉴定方面具有丰富经验的分子遗传团队。这支研究团队将招募迄今为止最大的RES患者队列，并首次以标准化的方式收集全面的临床、电生理和家谱数据。将利用包括大规模CNV分析和下一代测序技术在内的广泛技术，在50个大家庭和500个零星病例中识别与癫痫障碍有关的新基因。这些技术将被应用于系统化的遗传工作流程，以简化分析效率。最后，将根据基因发现进行基因型-表型关联，以确定新的疾病实体。这一倡议由10个欧洲合作伙伴和4个国际合作伙伴组成，其跨学科特征和规模是前所未有的。这种CRP有一个雄心勃勃的目标，就是要确定相当一部分罕见癫痫综合征患者的遗传基础。因此，我们期望这一C反应蛋白代表癫痫障碍遗传学研究中的一个里程碑。

The epilepsies are common neurological disorders with a strong genetic impact. Consequently, understanding the genetic basis of seizure disorders will provide novel insights into the underlying pathophysiology and result in novel diagnostic and therapeutic avenues. This collaborative research project will focus on the Rare Epilepsy Syndromes, an umbrella term for a group of familial epilepsies and epileptic encephalopathies, many of which represent severe and therapy-resistant epilepsies. Therefore, particularly in RES, novel strategies for treatment are urgently warranted. With respect to genetic risk factors, RES often represent extreme phenotypes. Genetic risk factors are particularly abundant and might lead the way for gene identification in more common epilepsies.This Collaborative Research Project (CRP) aims to decipher the genetic basis of many RES using a multinational large-scale approach, bringing together the expertise of epileptologists with access to large patient cohorts and molecular genetic teams with a vast experience in locus and gene identification.Collectively, this team of researchers will recruit the largest cohort of patients with RES to date and, for the first time, collect comprehensive clinical, electrophysiological and genealogical data in a standardized way. Novel genes for seizure disorders will be identified in 50 large families and 500 sporadic cases using broad range of technologies including large-scale CNV analysis and next-generation sequencing techniques. These technologies will be applied in a systematic genetic workflow to streamline analysis efficiency. Finally, genotype-phenotype correlation will be performed to identify novel disease entities based on genetic findings.The interdisciplinary character and scale of this initiative comprising 10 European partners and 4 international partners is unprecedented. This CRP has the ambitious goal to identify the genetic basis in a substantial fraction of patients with Rare Epilepsy Syndromes. Therefore, we expect this CRP to represent a milestone in genetic research in seizure disorders.