The molecular and genetic basis of myoclonic epilepsy

肌阵挛性癫痫的分子和遗传基础

• 批准号: 7114320
• 负责人: LOUIS J. PTACEK
• 金额: $ 35.14万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7114320
• 关键词: antiserum; artificial chromosomes; clinical research; complementary DNA; enzyme linked immunosorbent assay; family genetics; gene expression; genetic library; genetic mapping; genetic markers; genetic polymorphism; genetic susceptibility; genetically modified animals; high performance liquid chromatography; human subject; laboratory mouse; linkage mapping; myoclonus epilepsy; neurogenetics; patient oriented research; phlebotomy; plasmids; protein structure function; restriction fragment length polymorphism; yeast two hybrid system

DESCRIPTION (provided by applicant): Juvenile myoclonic epilepsy (JME) is among the commonest of the childhood epilepsies. Despite the recognition of strong genetic factors, molecular characterization of JME has thus far been unsuccessful. This may be due, in part, to genetic and clinical heterogeneity that is present in this disorder. Familial adult myoclonic epilepsy (FAME) is a rare idiopathic generalized epilepsy characterized by autosomal dominant inheritance, adult onset, varying degrees of myoclonus in the limbs, rare tonic-clonic seizures and a benign course. We have recently localized a gene for this disorder to chromosome 8q24.1. The objective of this research is to identify the gene responsible for FAME and to characterize the protein's role in this disorder specifically and in neuroexcitability more generally. This objective will be attained using several concurrent methods. First, the region corresponding to the FAME locus is being positionally cloned using bacterial artificial chromosomes and cosmids. Secondly, new polymorphic markers will be examined across the region to identify a shared haplotype between our FAME families. Finally, putative cDNAs identified through the EST database or through screening cDNA libraries, will be examined for mutations. Upon the identification of the FAME gene, appropriate cellular, biochemical, and physiological investigations will be performed to characterize the function of the FAME protein. Mouse models of FAME can then be created and will allow investigations of pathogenesis in vivo. These experiments will take place in a molecular genetics laboratory geared specifically towards experiments of this nature.

描述（由申请人提供）：少年肌阵挛性癫痫（JME）是儿童癫痫中最常见的癫痫之一。尽管认识到强遗传因素，但迄今为止，JME的分子表征尚未成功。这可能部分归因于这种疾病中存在的遗传和临床异质性。家族性成年肌阵挛性癫痫（名望）是一种罕见的特发性癫痫病，其特征在于常染色体显性遗传，成人发作，四肢中的肌阵挛程度不同，罕见的突变性癫痫发作和良性疗程。我们最近将这种疾病的基因定位为8q24.1染色体。这项研究的目的是确定导致名望的基因，并更普遍地表征蛋白质在该疾病中的作用。该目标将使用多种并发方法实现。首先，使用细菌人造染色体和宇宙染色体将与名望基因座相对应的区域定位。其次，将在整个地区检查新的多态标记，以确定我们名望家庭之间的共同单倍型。最后，将检查通过EST数据库或筛选cDNA库鉴定的假定cDNA以进行突变。在鉴定成名基因后，将进行适当的细胞，生化和生理研究，以表征名望蛋白的功能。然后可以创建成名的小鼠模型，并允许在体内进行发病机理研究。这些实验将发生在专门针对这种性质实验的分子遗传学实验室中。

项目成果

Episodic neurologic disorders: syndromes, genes, and mechanisms.

• DOI: 10.1146/annurev-neuro-062012-170300
• 发表时间: 2013-07
• 期刊: Annual review of neuroscience
• 影响因子: 13.9
• 作者: Jonathan F. Russell;Ying-Hui Fu;L. Ptáček

Familial cortical myoclonus with a mutation in NOL3.

• DOI: 10.1002/ana.23666
• 发表时间: 2012-08
• 期刊: ANNALS OF NEUROLOGY
• 影响因子: 11.2
• 作者: Russell, Jonathan F.;Steckley, Jamie L.;Coppola, Giovanni;Hahn, Angelika F. G.;Howard, MacKenzie A.;Kornberg, Zachary;Huang, Alden;Mirsattari, Seyed M.;Merriman, Barry;Klein, Eric;Choi, Murim;Lee, Hsien-Yang;Kirk, Andrew;Nelson-Williams, Carol;Gibson, Gillian;Baraban, Scott C.;Lifton, Richard P.;Geschwind, Daniel H.;Fu, Ying-Hui;Ptacek, Louis J.
• 通讯作者: Ptacek, Louis J.

The genetics of the human circadian clock.

• DOI: 10.1016/b978-0-12-387690-4.00007-6
• 发表时间: 2011
• 期刊: Advances in genetics
• 作者: Luoying Zhang;Christopher R. Jones;L. Ptáček;Ying-Hui Fu