MULTICENTER STUDY OF IDIOPATHIC GENERALIZED EPILEPSY

特发性全身性癫痫的多中心研究

• 批准号: 6743099
• 负责人: DAVID A. GREENBERG
• 金额: $ 103.19万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-01-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6743099
• 关键词: adolescence (12-20); blood chemistry; clinical research; cooperative study; disease /disorder classification; disease /disorder onset; electroencephalography; family genetics; gene expression; gene frequency; gene interaction; generalized seizures; genetic markers; genetic polymorphism; genotype; human genetic material tag; human subject; linkage mapping; myoclonus epilepsy; nervous system disorder epidemiology; neurogenetics; polymerase chain reaction; racial /ethnic difference

DESCRIPTION (Applicant's Abstract): This study will identify the loci involved in the expression of idiopathic generalized epilepsy (IGE) and investigate their interactions. In the previous grant period, we: 1) Completed a genome scan for loci of IGE; 2) Discovered at least 4 locations of genes for IGE; 3) Demonstrated and partly resolved heterogeneity in Juvenile Myoclonic Epilepsy (JME); 4) Narrowed the number of candidate loci for EJM1 to seven; 5) Found evidence that JME may be different in Caucasians and non-Caucasians. Pursuing these findings, we have the following aims: 1. Ascertain families with adolescent-onset forms of IGE. 2. Test for linkage heterogeneity at the loci on chromosomes 5, 8, and 18. 3. Test for further evidence of linkage at loci with promising but less significant lod scores on chromosomes 6q and 1. 4. Determine the relationship between genotype and seizure expression, correlating the linkage signal with the seizure types in the families. 5. Test whether non-EJM1 forms of JME map to chromosome 6q. 6. Test whether the frequency of JME due to EJM1 in non-Caucasians is the same as in Caucasians. 7. Determine which of 7 candidate loci is EJM1. 8. Fine-mapping on the candidate regions on chromosomes 5, 8, and 18. The exciting previous results suggest we may now have located many of the genes for adolescent-onset IGE. We will use the linkage and population studies to determine how interactions between the loci influence seizure type and, by eventually determining the actual disease loci, delineate how these loci produce seizures.

描述（申请人摘要）：本研究将确定涉及的基因座 在特发性全身性癫痫（IGE）的表达中， 他们的互动。在上一个资助期，我们：1）完成了一个基因组 IGE基因位点扫描; 2）发现至少4个IGE基因位点; 3） 在青少年肌阵挛性癫痫中证实和部分解决的异质性 (JME)4）将EJM 1的候选基因座的数量缩小到7个; 5）发现 有证据表明，JME可能是不同的高加索人和非高加索人。追求 根据这些研究结果，我们有以下目的： 1.确定有反复发作型IGE的家系。2.联动试验 第5、8和18号染色体上基因座的异质性。3.测试进一步 在有希望但不太显著的lod分数的位点上的连锁证据， 染色体6 q和1。4.确定基因型与 癫痫发作表达，将连锁信号与癫痫发作类型相关联， 那些家庭5.测试JME的非EJM 1形式是否映射到染色体6 q。6. 测试非白种人中EJM 1引起的JME的频率是否与 在高加索人。7.确定7个候选基因座中的哪一个是EJM 1。8.精细映射 5号8号和18号染色体上的候选区域。令人兴奋的前 结果表明，我们现在可能已经定位了许多与癫痫发作有关的基因， IGE。我们将使用联系和人口研究，以确定如何 基因座之间的相互作用影响癫痫发作类型， 确定实际的疾病位点，描述这些位点如何产生癫痫发作。