title: Germ-line mutation of KCNQ2, p.R213W, in a Japanese family with benign familial neonatal convulsion.
abstract: BACKGROUND
  Benign familial neonatal convulsion (BFNC) is an autosomal-dominantly inherited epilepsy of neonates. The KCNQ2 and KCNQ3 genes have been cloned as the responsible genes for BFNC. Detection of mutations in these genes is helpful for confirmation of BFNC or differential diagnosis of convulsive disorders in the neonatal period.
  
  
  METHODS
  A Japanese family with BFNC was investigated. Two siblings were clinically diagnosed as having BFNC. KCNQ2 and KCNQ3 were screened for mutations using a combination of polymerase chain reaction and denaturing high-performance liquid chromatography. Nucleotide substitutions were confirmed by direct sequencing.
  
  
  RESULTS
  In the affected siblings a C-to-T heterozygous substitution was detected at nucleotide 683 (c.683C>T) in KCNQ2, leading to substitution of arginine with tryptophan at amino acid position 213 (p.R213W) in the S4 voltage-sensing domain of the KCNQ2 protein. The detected mutation may disrupt this highly conserved region among potassium channel proteins. The c.683C>T substitution in KCNQ2 was not present in the parents. KCNQ3 was also analyzed and a single nucleotide polymorphism, c.1241A>G (National Center for Biotechnology Information (NCBI), SNP ID: rs2303995), was detected in the index family.
  
  
  CONCLUSIONS
  Two siblings with BFNC had a novel heterozygous missense mutation, p.R213W, in KCNQ2. This mutation may affect potassium gating, leading to neuronal excitability or convulsions in the patients. Furthermore, neither of the parents had the p.R213W mutation, indicating that it was a germ-line mutation. The possibility of recurrence of such a germ-line mutation in the next siblings should be explained during genetic counseling.
authors: Department of Public Health, Kobe University Graduate School of Medicine, Kobe, Japan.
authors: Ahmad H
authors: AH
authors: Sadewa
authors: Teguh H
authors: TH
authors: Sasongko
authors: Myeong J
authors: MJ
authors: Lee
authors: Kazunari
authors: K
authors: Daikoku
authors: Akiyo
authors: A
authors: Yamamoto
authors: Takemi
authors: T
authors: Yamasaki
authors: Shigenori
authors: S
authors: Tanaka
authors: Masafumi
authors: M
authors: Matsuo
authors: Hisahide
authors: H
authors: Nishio
mesh_terms: D044466:Asian People / Q000235:genetics*; D020936:Epilepsy, Benign Neonatal / Q000208:ethnology / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D051658:KCNQ2 Potassium Channel / Q000235:genetics*; D008297:Male
chemical_list: D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human