Genetic study of epilepsies and febrile convulsions

Epilepsy is a neurolagical disorder characterized by recurring seizures. Epilepsy affects more than0.5% of the world's population and has a large genetic component the most common human geneticepilepsies display a complex pattern of inheritance and the身份of the susceptibility genes islargely unknown.This report summarizes our own discovery of two novel mutations in the genes ofautosomal dominant nocturnal frontal lobe epilepsy （ADNFLE）和benign familial neonatal convulsions(bfnc),A "C" to and our mapping of the genetic locus of benign adult familial myoclonic epilepsy （BAFME）“T” exchange (C752T)was found in exon 5 of the CHRNA4 gene on one allele of individuals withADNFLE. C752T replaced Ser - D1252 - D1 in the second membrane spanning domain (M2) of CHRNA4 with aleucine. Ser - D1252 - D1是conserved characteristically in the α4 subunit acetylcholine recepter，a α4 subunit acetylcholine receptor that is considered to play an important role in the channel我们screened six Japanese families with BFNC for mutations of KCNQ3，和发现a T to C exchange （cDNA925T> on one allele in affected individuals in a family but not on）200 alleles of健康志愿者。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 familythis study.The present results support a hypothesis that some types of idiopathic epilepsy are a初步of channelopathy.understanding gained from work in this areas of epilepsy research is not onlyallowing characterization of the molecular and physiologic basis of these epilepsiesbut also ultimately sheds light on our understanding of pathophysiology of more common epilepsiesand promises new vistas of AED and may benefit large numbers of affected individuals。

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.