Genetics of Epilepsy in Mali (GENEP-Mali)

马里癫痫遗传学 (GENEP-Mali)

基本信息

批准号：
10684266
负责人：
SAQUIB A LAKHANI
金额：
$ 47.44万
依托单位：
UNIV OF SCIENCES, TECH & TECH OF BAMAKO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-15 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10684266
关键词：
Achievement Address Affect Africa Africa South of the Sahara African Antiepileptic Agents Anxiety Applications Grants Area Attention Awareness Basic Science Bioinformatics Biological Models Brain Injuries CRISPR/Cas technology Candidate Disease Gene Caring Child Childhood Clinical Collaborations Counseling Critical Illness DNA DNA sequencing Data Developing Countries Development Diagnosis Disease Disparity Economic Burden Economics Education Electroencephalography Epidemiology Epilepsy Equity Evaluation Family Foundations Fright Future Genes Genetic Genetic Predisposition to Disease Genetic Research Genomics Genotype Goals Health Personnel Inequity Infrastructure Maintenance Mali Mental Depression Mentors Mentorship Methodology Neurologic Patients Persons Pharmaceutical Preparations Phenotype Population Prognosis Provider Public Health Public Policy Quality of life Rana Rare Diseases Reporting Research Research Infrastructure Research Personnel Resources Sampling Schedule Scientist Seizures Site Visit Students Surveys Testing Training Translational Research Universities Variant Visit Work Xenopus burden of illness candidate identification care providers care seeking community engagement design diagnostic value efficacy evaluation experimental study genetic analysis genetic element genetic variant imaging study improved in vivo Model insight low and middle-income countries nervous system disorder neurogenetics next generation next generation sequencing novel patient engagement prevent programs psychosocial public education recruit social social stigma tool

项目摘要

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.

概括癫痫是最常见的神经系统疾病之一，影响多达 5000 万人全球范围内，其中80%以上生活在发展中国家。尽管事实上~70%的人对药物治疗有反应的癫痫 (PWE) 患者中，多达十分之九的癫痫患者仍未得到治疗非洲，导致脑损伤和相关后遗症。此外，癫痫还具有严重的社会心理影响。由于其耻辱而造成的负担，使许多 PWE 无法寻求护理，并导致严重的个人、社会和经济危害。有趣的是，人们越来越认识到癫痫的遗传原因，受到下一代 DNA 测序 (NGS) 蓬勃发展的推动。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方案马里应对癫痫的方法。 1) 教育一线医疗保健提供者识别和治疗癫痫，以努力缩小马里巨大的治疗差距。 2) 仔细按顺序对 PWE 进行表型分析了解马里的癫痫状况。 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 中获取特定的 DNA 样本 NGS 表型，并分析数据以确定候选致病基因。 5) 测试这些基因脊椎动物模型系统，热带爪蟾。此外，该项目的一个关键组成部分是 6) 马里学生参观耶鲁大学并接受 NGS 分析/生物信息学和热带 X 线虫实验培训。最后，7）耶鲁大学的一个团队将定期前往马里进行实地考察，以利用他们的专业知识来扩大当地业务生物信息能力并建立热带 X.tropicis 脊椎动物实验设施。这个广泛的方法，包括临床、流行病学、遗传学和基础科学方面，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。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Biallelic CRELD1 variants cause a multisystem syndrome, including neurodevelopmental phenotypes, cardiac dysrhythmias, and frequent infections.

双等位基因 CRELD1 变异会导致多系统综合征，包括神经发育表型、心律失常和频繁感染。

DOI：
发表时间：
2024-02
期刊：
影响因子：
0
作者：
Jeffries, Lauren;Mis, Emily K;McWalter, Kirsty;Donkervoort, Sandra;Brodsky, Nina N;Carpier, Jean;Ji, Weizhen;Ionita, Cristian;Roy, Bhaskar;Morrow, Jon S;Darbinyan, Armine;Iyer, Krishna;Aul, Ritu B;Banka, Siddharth;Chao, Katherine R;Co
通讯作者：
Co

Pentanucleotide Repeat Insertions in RAI1 Cause Benign Adult Familial Myoclonic Epilepsy Type 8.

RAI1 中的五核苷酸重复插入会导致良性成人家族性肌阵挛癫痫 8 型。

DOI：
10.1002/mds.29654
发表时间：
2023-11-22
期刊：
Movement Disorders
影响因子：
8.6
作者：
Patra Yeetong;M. E. Dembélé;M. Pongpanich;L. Cissé;C. Srichomthong;A. B. Maiga;K. Dembélé;Adjima Assaw
通讯作者：
Adjima Assaw