Genetics of the rare epilepsy syndromes

癫痫是一种常见的神经系统疾病，具有很强的遗传影响。因此，了解癫痫发作疾病的遗传基础将提供新的见解，潜在的病理生理学，并导致新的诊断和治疗途径。该合作研究项目将重点关注罕见癫痫综合征，这是一组家族性癫痫和癫痫性脑病的总称，其中许多代表严重和耐药性癫痫。因此，特别是在RES中，迫切需要新的治疗策略。关于遗传风险因素，RES通常代表极端表型。遗传风险因素特别丰富，可能导致更常见癫痫的基因鉴定。该合作研究项目（CRP）旨在使用多国大规模方法破译许多RES的遗传基础，汇集了癫痫学家的专业知识，可以访问大型患者队列和分子遗传学团队，在基因座和基因鉴定方面拥有丰富的经验。这组研究人员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。将使用广泛的技术，包括大规模CNV分析和下一代测序技术，在50个大家族和500个散发病例中鉴定癫痫发作疾病的新基因。这些技术将应用于系统的遗传工作流程，以提高分析效率。最后，将进行基因型-表型相关性分析，以根据遗传学发现确定新的疾病实体。这项由10个欧洲合作伙伴和4个国际合作伙伴组成的倡议的跨学科性质和规模是前所未有的。该CRP的雄心勃勃的目标是确定相当一部分罕见癫痫综合征患者的遗传基础。因此，我们希望这种CRP代表癫痫发作疾病遗传学研究的里程碑。

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.