Genetics of Rolandic Epilepsy

罗兰迪克癫痫的遗传学

• 批准号: 6875995
• 负责人: DEB K PAL
• 金额: $ 45.37万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-24 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6875995
• 关键词: clinical research; electroencephalography; epilepsy; gene mutation; genetic mapping; genetic susceptibility; genome; genotype; human subject; linkage mapping; neurogenetics; neuropsychological tests; neuropsychology; nucleic acid sequence; patient oriented research

DESCRIPTION (provided by applicant): The goal of this research is to find the genes underlying Rolandic epilepsy (RE), a developmental focal epilepsy of complex genetic inheritance. RE is the most common epilepsy of childhood and is frequently associated with specific neuropsychological deficits (NPDs), an observation that is not widely appreciated by treating clinicians or by teachers. The NPDs, as well as a subclinical EEG trait, are also found in siblings of RE patients, suggesting RE is caused by a few genes of major effect, a situation for which linkage and association analysis are ideal. We propose to use linkage analysis to identify susceptibility loci for RE and NPDs, and use modern molecular methods and association analysis to pinpoint and identify disease genes at these loci. The three specific aims of the proposal are: (1) to collect detailed clinical, EEG and neuropsychological data and DNA samples from at least 100 families with a typical RE proband. We will use stringent eligibility criteria, and an expert panel to subclassify cases; (2) to perform a genome-wide linkage analysis screen to identify susceptibility loci for RE. We will test, using linkage analysis, the hypotheses that: i) the RE+/-EEG trait and NPDs are manifestations of the same genotype; ii) subtypes of RE, based on diurnal pattern or seizure frequency, represent genetically heterogeneous forms; iii) large, densely affected RE pedigrees have different inheritance from RE found in nuclear families; iv) RE is linked to candidate loci for idiopathic generalized or focal epilepsies; (3) Identify genes and specific mutations at these susceptibility loci that predispose to RE, and that contribute to the expression of clinical, treatment and cognitive outcomes. We will perform precise gene mapping and mutation detection principally using recombination analysis, dense SNP mapping, haplotype reconstruction and DNA sequencing. Finding RE genes is important because of its high incidence and currently unknown etiology. More importantly, the cause, population incidence, and prognosis of NPDs associated with RE is unknown. We can use genotype-phenotype correlations from our uniquely valuable resource for molecular diagnostic tools to improve patient care and to plan early intervention. Furthermore, genetic discoveries from this research will stimulate discoveries in related severe idiopathic focal childhood epilepsies and neurodevelopmental biology.

描述（由申请人提供）：本研究的目的是寻找罗兰dic癫痫（RE）的基因，这是一种复杂遗传的发育局灶性癫痫。RE是儿童期最常见的癫痫，通常与特异性神经心理缺陷（npd）相关，这一观察结果并未得到治疗临床医生或教师的广泛认可。在RE患者的兄弟姐妹中也发现了npd和亚临床脑电图特征，这表明RE是由少数主要基因引起的，这种情况是连锁和关联分析的理想选择。我们建议使用连锁分析来确定RE和npd的易感位点，并使用现代分子方法和关联分析来确定这些位点上的疾病基因。