title: A de novo KCNQ2 mutation detected in non-familial benign neonatal convulsions.
abstract: BACKGROUND
  The underlying genetic abnormalities of rare familial idiopathic epilepsy have been identified, such as mutation in KCNQ2, a K(+) channel gene. Yet, few genetic abnormalities have been reported for commoner epilepsy, i.e., sporadic idiopathic epilepsy, which share a phenotype similar to those of familial epilepsy.
  
  
  OBJECTIVE
  To search for the genetic cause of seizures in a girl with the diagnosis of non-familial benign neonatal convulsions, and define the consequence of the genetic abnormality identified.
  
  
  METHODS
  Genetic abnormality was explored within candidate genes for benign familial neonatal and infantile convulsions, such as KCNQ2, 3, 5, KCNE2, SCN1A and SCN2A. The electrophysiological properties of the channels harboring the identified mutation were examined. Western blotting and immunostaining were employed to characterize the expression and intracellular localization of the mutant channel molecules.
  
  
  RESULTS
  A novel heterozygous mutation (c.910-2delTTC or TTT, Phe304del) of KCNQ2 was identified in the patient. The mutation was de novo verified by parentage analysis. The mutation was associated with impaired functions of KCNQ K(+) channel. The mutant channels were expressed on the cell surface.
  
  
  CONCLUSIONS
  The mutant Phe304del of KCNQ2 leads to null function of the KCNQ K(+) channel but the mutation does not alter proper channel sorting onto the cell membrane. Our findings indicate that the genes responsible for rare inherited forms of idiopathic epilepsy could be also involved in sporadic forms of idiopathic epilepsy and expand our notion of the involvement of molecular mechanisms in the more common forms of idiopathic epilepsy.
authors.affiliation: Department of Pediatrics, School of Medicine, Fukuoka University, 45-1, 7-chome Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ishii
authors.forename: Goryu
authors.initials: G
authors.lastname: Fukuma
authors.forename: Akira
authors.initials: A
authors.lastname: Uehara
authors.forename: Tasuku
authors.initials: T
authors.lastname: Miyajima
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Makita
authors.forename: Akiyo
authors.initials: A
authors.lastname: Hamachi
authors.forename: Midori
authors.initials: M
authors.lastname: Yasukochi
authors.forename: Takahito
authors.initials: T
authors.lastname: Inoue
authors.forename: Sawa
authors.initials: S
authors.lastname: Yasumoto
authors.forename: Motohiro
authors.initials: M
authors.lastname: Okada
authors.forename: Sunao
authors.initials: S
authors.lastname: Kaneko
authors.forename: Akihisa
authors.initials: A
authors.lastname: Mitsudome
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirose
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D004252:DNA Mutational Analysis / Q000379:methods; D004569:Electroencephalography; D020936:Epilepsy, Benign Neonatal / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D051658:KCNQ2 Potassium Channel / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014162:Transfection
chemical_list: D051658:KCNQ2 Potassium Channel