MULTICENTER STUDY OF IDIOPATHIC GENERALIZED EPILEPSY

特发性全身性癫痫的多中心研究

• 批准号: 6131105
• 负责人: DAVID A. GREENBERG
• 金额: $ 94.32万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 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 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6131105
• 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（申请人的摘要）：本研究将确定所涉及的基因座 特发性全身性癫痫 (IGE) 的表达并调查 他们的互动。在上一个资助期内，我们：1）完成了基因组 扫描 IGE 基因座； 2）发现至少4个IGE基因位置； 3） 已证实并部分解决了青少年肌阵挛性癫痫的异质性 （JME）； 4) 将EJM1的候选位点数量缩小至7个； 5) 找到 有证据表明 JME 在白人和非白人中可能有所不同。追求 根据这些发现，我们有以下目标： 1. 确定患有青少年发病型 IGE 的家庭。 2. 联动测试 5、8、18 号染色体位点的异质性。 3. 进一步测试 有证据表明基因座与有希望但不太显着的 lod 分数存在关联 染色体 6q 和 1。 4. 确定基因型和 1 号染色体之间的关系 癫痫发作表达，将连锁信号与癫痫发作类型相关联 家人。 5. 测试 JME 的非 EJM1 形式是否映射到染色体 6q。 6. 测试非白种人中由 EJM1 引起的 JME 频率是否与 在白种人中。 7. 确定 7 个候选基因座中哪一个是 EJM1。 8. 精细映射 在 5、8 和 18 号染色体上的候选区域上。 结果表明我们现在可能已经找到了许多青春期发病的基因 IGE。我们将利用联系和人口研究来确定如何 位点之间的相互作用影响癫痫类型，并最终 确定实际的疾病位点，描述这些位点如何产生癫痫发作。