title: A novel mutation of CHRNA4 responsible for autosomal dominant nocturnal frontal lobe epilepsy.
abstract: OBJECTIVE
  To identify the mutation responsible for autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) in a nonwhite family.
  
  
  BACKGROUND
  ADNFLE is newly recognized as an entity of idiopathic partial epilepsy. Recently, two different mutations of the neuronal nicotinic acetylcholine receptor alpha4 subunit (CHRNA4) gene were identified in a white family as a cause of ADNFLE.
  
  
  METHODS
  Four affected and three unaffected individuals in three generations of a Japanese family with ADNFLE, and 100 unrelated healthy Japanese volunteers were studied. Clinical features and EEG findings in affected individuals were consistent with those of ADNFLE reported in white families with ADNFLE. Mutations within the CHRNA4 gene were screened for using single-strand conformation polymorphism analysis (SSCA) and were determined by direct sequencing. The mutation identified was sought in volunteers by the amplification refractory mutation system.
  
  
  RESULTS
  A C-to-T exchange (C755T) was found in exon 5 of the CHRNA4 gene on one allele of affected individuals. C755T segregated in affected individuals and was not found in 200 alleles obtained from the volunteers. C755T replaced serine 252 (Ser252) in the second membrane-spanning domain (M2) of CHRNA4 with a leucine. Ser252 is conserved characteristically in the alpha-subunit of acetylcholine receptor and is considered to play an important role in channel function.
  
  
  CONCLUSIONS
  C755T is a novel missense mutation of the CHRNA4 gene causing autosomal dominant nocturnal frontal lobe epilepsy in this Japanese family.
authors.affiliation: Department of Pediatrics, School of Medicine, Fukuoka University, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hirose
authors.forename: H
authors.initials: H
authors.lastname: Iwata
authors.forename: H
authors.initials: H
authors.lastname: Akiyoshi
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: K
authors.initials: K
authors.lastname: Wada
authors.forename: S
authors.initials: S
authors.lastname: Kaneko
authors.forename: A
authors.initials: A
authors.lastname: Mitsudome
mesh_terms: D002940:Circadian Rhythm; D017034:Epilepsy, Frontal Lobe / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000502:physiology*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011978:Receptors, Nicotinic / Q000235:genetics*; D012016:Reference Values
chemical_list: D011978:Receptors, Nicotinic