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Genetic study of epilepsies and febrile convulsions

癫痫和热性惊厥的遗传学研究

基本信息

批准号：
09470206
负责人：
KANEKO Sunao
金额：
$ 8.32万
依托单位：
Hirosaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470206/
关键词：
Epilepsy Epilepsy genes autosomal dominant nocturnal frontal lobe epilepsy benign familial neonatal convulsions benign adult familial myoclonic epilepsy ion channel

项目摘要

Epilepsy is a neurolagical disorder characterized by recurring seizures. Epilepsy affects more than 0.5% of the world's population and has a large genetic component. The most common human genetic epilepsies display a complex pattern of inheritance and the identity of the susceptibility genes is largely unknown.This report summarizes our own discovery of two novel mutations in the genes of autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and benign familial neonatal convulsions (BFNC), and our mapping of the genetic locus of benign adult familial myoclonic epilepsy (BAFME). A ""C"" to ""T"" exchange (C752T)was found in exon 5 of the CHRNA4 gene on one allele of individuals with ADNFLE. C752T replaced SerィイD1252ィエD1 in the second membrane spanning domain (M2) of CHRNA4 with a leucine. SerィイD1252ィエD1 is conserved characteristically in the α4 subunit acetylcholine recepter, a α4 subunit acetylcholine receptor that is considered to play an important role in the channel function. We screened six Japanese families with BFNC for mutations of KCNQ3, and found a T to C exchange (cDNA925T> on one allele in affected individuals in a family but not on 200 alleles of healthy volunteers. cDNA925T>C replaced Try262, a conserved residue within P-loop of the KCNQ family, with an Arg (W262R). The gene for BAPME was assigned to chromosome 8q23.3-q24.1 in a Japanese family by this study.The present results support a hypothesis that some types of idiopathic epilepsy are a form of channelopathy.Understanding gained from work in this areas of epilepsy research is not only allowing characterization of the molecular and physiologic basis of these epilepsies, but also ultimately sheds light on our understanding of pathophysiology of more common epilepsies, and promises new vistas of AED and may benefit large numbers of affected individuals.

癫痫是一种以反复发作为特征的神经语言障碍。癫痫影响着世界上0.5%以上的人口，并且有很大的遗传成分。人类最常见的遗传性癫痫表现出一种复杂的遗传模式，其易感基因的一致性在很大程度上尚不清楚。本文总结了我们在常染色体显性遗传性夜间额叶癫痫(ADNFLE)和良性家族性新生儿惊厥(BFNC)基因中发现的两个新突变，以及我们对良性成人家族性肌阵挛癫痫(BAFME)的基因定位。在1个ADNFLE患者的CHRNA4基因第5外显子上发现了“C”到“T”的交换(C752T)。C752T在CHRNA4的第二膜跨区(M2)用亮氨酸取代了SerD1252ィエD1。SerィイD1252ィエD1在α4亚单位乙酰胆碱受体中保守，这是一种被认为在通道功能中发挥重要作用的α4亚单位乙酰胆碱受体。我们对6个BFNC日本家系进行了KCNQ3基因突变的筛查，发现在一个家系中的一个患病个体的一个等位基因上存在T-C交换(cDNA925T&GT；)，而在200个健康志愿者的等位基因上没有发现。CDNA925T&gt；C用Arg(W262R)取代了KCNQ家族P-环中的保守残基Try262。本研究将BAPME基因定位于一个日本家系的染色体8q23.3-q24.1。目前的研究结果支持一种假说，即某些类型的特发性癫痫是一种通道病。在癫痫研究领域的工作不仅有助于表征这些癫痫的分子和生理基础，而且最终有助于我们对更常见癫痫的病理生理学的理解，并有望为AED提供新的前景，并可能使大量患者受益。