Genetic Epidemiology of Seizure Disorders In Rochester

描述(申请人提供)：已取得实质性进展 近年来在位置克隆癫痫易感基因中的异常 有孟德尔传播形式的家庭。然而，人们对此知之甚少。 不同癫痫综合征的遗传效应大小 群体，或由特定基因产生的临床表型范围 机械装置。我们建议在一项基于人口的研究中解决这些问题 共同和不同的基因对特定的癫痫发作障碍的影响以及 癫痫综合征，使用罗切斯特-奥姆斯特县记录的数据 联动项目。病例先证者将是1920年或以后出生的所有罗切斯特居民 后来，癫痫的发病率或孤立的无缘无故的发作 1935-1994年(N=1056)。控制先驱将是没有无缘无故的个人 根据出生年份、种族和年龄长短与病例相匹配 罗切斯特住院医生。诊断和分类将基于以下方面的审查 医疗记录，辅以半结构化诊断性面谈，以确保 这些数据是关于基本临床特征的系统收集。 病例的一级亲属和癫痫发作障碍的信息 控制措施将通过审查亲属的医疗记录来收集， 辅以先证者面谈。血液样本将从活人身上采集 候选基因关联研究的病例和对照。数据将是 用于评估癫痫的哪些临床特征最有可能预测 遗传易感性是否也提高了遗传对癫痫的影响 其他癫痫发作障碍的风险(孤立的无缘性癫痫、发热 抽搐和其他急性症状性癫痫)，以及是否不同 临床定义的癫痫综合征有相同或不同的基因 影响。雌性和雄性后代癫痫发作障碍的风险 将对先证者进行比较，以探索先前观察到的母体效应 癫痫。一组候选基因，编码电压门控或 配基门控离子通道将从直接和间接两个方面进行研究 使用单核苷酸的(单倍型或基于标记的)关联测试 多态(SNPs)。

DESCRIPTION (provided by applicant): Substantial progress has been made recently in positional cloning of epilepsy susceptibility genes in unusual families with Mendelian forms of transmission. However, little is known about the magnitude of genetic effects on different epilepsy syndromes in the population, or the range of clinical phenotypes produced by specific genetic mechanisms. We propose to address these questions in a population-based study of the shared and distinct genetic influences on specific seizure disorders and epilepsy syndromes, using data from the Rochester-Olmsted County Records Linkage Project. Case probands will be all Rochester residents born in 1920 or later with incidence of epilepsy or an isolated unprovoked seizure from 1935-1994 (N=1056). Control probands will be individuals without unprovoked seizures, matched to the cases by birth year, ethnicity, and length of Rochester residency. Diagnosis and classification will be based on review of medical records, supplemented by semistructured diagnostic interviews to ensure that data are collected systematically on essential clinical features. Information on seizure disorders in the first-degree relatives of cases and controls will be collected by review of the medical records of the relatives, supplemented by proband interviews. Blood samples will be collected from living cases and controls for candidate gene association studies. The data will be used to assess which clinical features of epilepsy are most likely to predict a genetic susceptibility whether the genetic influences on epilepsy also raise risk for other seizure disorders (isolated unprovoked seizures, febrile convulsions, and other acute symptomatic seizures), and whether different clinically-defined epilepsy syndromes have shared or distinct genetic influences. Risks of seizure disorders in the offspring of female and male probands will be compared to explore the previously observed maternal effect in epilepsy. A set of candidate genes encoding either voltage-gated or ligand-gated ion channels will be investigated in both direct and indirect (haplotype or marker-based) association tests utilizing single nucleotide polymorphisms (SNPs).