Genetic study of epilepsies and febrile convulsions

癫痫是一种由反复发作引起的神经性紊乱特征。Epilepsy的影响超过了世界人口的0.5%，而且它有一个较大的遗传成分。最常见的人类基因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 fron·lobe epsy（ADNFLE） and benign fal neonatal convulsions （BFNC）， and our mapping of the genetic locus of benign adult fal myoclonic epilepsy （BAFME）。A "C" to "T" exchange （C752T）was found in exon 5 of the CHRNA4gene on one allele of individuals with ADNFLE。C752 T replaced Ser D1252エD1 in the second？brane spanning domain （M2） of CHRNA4 with a leucine。Ser-D1252-D1 is conserved characteristically in the rp4 subunit acetylcholine recepter， a rp4 subunit acetylcholine receptor that is considered to play an important role in the channel function。我们为KCNQ 3的突变筛选了六个日本家族的BFNC，并在一个家族中找到了一个T到C交换（cDNA 925 T>关于一个受影响的个人的信号，但不是关于200个健康波动的信号。cDNA 925 T>C替换尝试262，在KCNQ家族的P回路内，与Arg （W262 R）一起使用。BAPME基因被分配到日本家族中的染色体8q23.3-q24.1，本研究的结果支持一个催眠，即某些类型的糖尿病发作是一种慢性病的形式。了解从在这一领域的癫痫研究中获得的工作不仅允许分子和生理学基础的特征化，而且还不能只允许这些癫痫发作的分子和生理学基础，但也有最充分的阴影照亮了我们对更常见的癫痫病学的理解，并承诺对AED进行新的观察，并可能对受影响的个人有好处。

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.