Genetics of Epilepsy in Mali (GENEP-Mali)

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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.