Genetics of Epilepsy in Mali (GENEP-Mali)

总结 癫痫是最常见的神经系统疾病之一，影响多达5000万人 世界上80%以上的人生活在发展中国家。尽管70%的人 癫痫（PWE）对药物治疗有反应，在10名患者中， 非洲，导致脑损伤和相关后遗症。此外，癫痫还具有严重的心理社会问题。 由于其耻辱感而造成的负担，使许多PWE无法寻求护理，并导致重大的个人， 社会和经济危害。有趣的是，癫痫的遗传原因越来越被认识到， 受下一代DNA测序（NGS）热潮的推动。然而，绝大多数遗传 研究忽略了撒哈拉以南非洲的人口。在这个项目中，我们提出了一个多管齐下的 在马里治疗癫痫的方法。1)教育一线医疗保健提供者识别和治疗 这是一项旨在缩小马里巨大治疗差距的计划。2)仔细表型PWE， 了解马里癫痫的情况。3)让PWE参与了解疾病的负担 通过使用定量和定性工具。4)从PWE获得DNA样本， 表型的NGS，并分析数据，以确定候选致病基因。5)测试这些基因在一个 脊椎动物模型系统，热带爪蟾。此外，这个项目还有一个关键组成部分， 学生访问耶鲁大学，并在NGS分析/生物信息学和X.热带实验 最后，耶鲁大学的一个团队将定期到马里进行实地考察，以利用他们的专业知识， 生物信息学能力，并建立一个X.用于脊椎动物实验的热带设施。这一广泛 包括临床、流行病学、遗传学和基础科学方面的方法将服务于以下单一目标： 更好地了解马里的癫痫病，以改善马里PWE的护理和生活质量。

SUMMARY Epilepsy is one of the most common neurological disorders, affecting as many as 50 million people worldwide with more than 80% of them living in developing countries. Despite the fact that ~70% of people with epilepsy (PWE) respond to medication therapy, epilepsy remains untreated in up to 9 in 10 patients in Africa, leading to brain damage and associated sequelae. In addition, epilepsy bears a heavy psychosocial burden due to its stigma, preventing many PWE from seeking care and leading to significant personal, social, and economic harm. Interestingly, genetic causes of epilepsy are being increasingly recognized, driven by the boom in next generation DNA sequencing (NGS). However, the vast majority of genetic research has ignored populations in sub-Saharan Africa. In this project, we propose a multi-pronged approach to tackling epilepsy in Mali. 1) Educate front-line healthcare providers to recognize and treat epilepsy in an effort to decrease the massive treatment gap in Mali. 2) Carefully phenotype PWE in order understand the landscape of epilepsy in Mali. 3) Engage PWE to understand the burden of the disease through the use of quantitative and qualitative tools. 4) Obtain DNA samples from PWE with specific phenotypes for NGS, and analyze the data to identify candidate causative genes. 5) Test these genes in a vertebrate model system, Xenopus tropicalis. In addition, this project has a key component for 6) Malian students to visit Yale University and train in NGS analysis/bioinformatics and X. tropicalis experiments. Finally, 7) a team from Yale will make scheduled site visits to Mali to lend their expertise to expand local bioinformatic capacity and to establish a X. tropicalis facility for vertebrate experiments. This broad approach, with clinical, epidemiologic, genetic, and basic science aspects, will serve the single goal of better understanding epilepsy in Mali in order to improve the care and quality of life of Malian PWE.