title: A novel mutation of the nicotinic acetylcholine receptor gene CHRNA4 in sporadic nocturnal frontal lobe epilepsy.
abstract: Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is known to be partly caused by mutations in the transmembrane domain (TM) 1-3 of the genes of the neuronal nicotinic acetylcholine receptor (nAChR) alpha4-subunit (CHRNA4), beta2-subunit (CHRNB2) and alpha2-subunit (CHRNA2). The more common cases of sporadic nocturnal frontal lobe epilepsy (NFLE) that are not differentiated from ADNFLE by phenotype have been found to be associated with the mutation of CHRNA4 reported in ADNFLE. In order to assess the genetic defects in NFLE, we performed a mutation screening in 33 unrelated patients with sporadic NFLE by amplifying and sequencing bidirectionally TM 1-3 of CHRNA4, CHRNB2 and CHRNA2 which contain the mutations reported in ADNFLE. In screening CHRNA4, we identified a novel mutation in one patient that causes a alpha4-R308H amino acid exchange outside the TM, and in the second intracellular loop between the third and fourth transmembrane domains. The mutation was not observed in 400 control chromosomes. No mutations were present in parts of CHRNB2 and CHRNA2.
authors.affiliation: Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Dong Dan, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Liwen
authors.initials: L
authors.lastname: Wu
authors.forename: Yue
authors.initials: Y
authors.lastname: Fang
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: He
authors.forename: Bingwei
authors.initials: B
authors.lastname: Peng
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.forename: Qi
authors.initials: Q
authors.lastname: Xu
mesh_terms: D000293:Adolescent; D000328:Adult; D001120:Arginine / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D017034:Epilepsy, Frontal Lobe / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006639:Histidine / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D011978:Receptors, Nicotinic / Q000235:genetics*; D055815:Young Adult
chemical_list: D001120:Arginine; D006639:Histidine; D011978:Receptors, Nicotinic