title: [A novel mutation in KCNQ2 gene causes benign familial infantile convulsions (BFIC) in a Chinese family].
abstract: OBJECTIVE
  Benign familial infantile convulsions (BFIC) is a form of idiopathic epileptic syndrome characterized by onset of afebrile seizures between 3 and 12 months of life, Spontaneous remission after several weeks or months, and autosomal dominant mode of inheritance. Previous linkage analysis in western countries defined three susceptible loci on chromosomes 19q12.0-13.1, 16p12-q12, and 2q23-31, but studies performed in several Chinese families with BFIC got negative results of these previously reported loci. The authors investigated the relation of voltage-gated potassium channel gene KCNQ2 to BFIC in a Chinese family and thus to understand the molecular pathogenesis of BFIC.
  
  
  METHODS
  A four-generation Chinese BFIC family was investigated. All the affected 17 members had similar pattern of seizures starting from 2 to 6 months of age. In 15 of them, the seizures disappeared spontaneously within the first year of life. The phenotype extended beyond infancy only in two patients. Blood sample was collected from the 41 family members and 75 unassociated normal individuals. Polymerase chain reaction (PCR)-DNA direct sequencing was performed to screen all exons and their flanking introns of KCNQ2 gene for mutation analysis. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was used to ascertain the co-segregation of genotype and phenotype and to exclude polymorphism.
  
  
  RESULTS
  PCR amplification and subsequent direct sequencing of KCNQ2 from the DNA of proband revealed a heterozygous guanine to thymine nucleotide exchange (G812T) in exon 5, leading to the substitution of glycine by valine at amino acid position 271 (G271V) of the predicted protein. The same mutation with a comparable localization has been previously described for KCNQ3 in benign familial neonatal convulsions (BFNC). The glycine at this position (G271) is located in pore region of KCNQ2 protein and is evolutionarily highly conserved. The same SSCP variant as that of the proband was shown in the rest of the affected members of this family but not in the unaffected members enrolled in the study of this family and all the 75 unrelated normal individuals.
  
  
  CONCLUSIONS
  Previously reported mutations of KCNQ2 were mainly identified in BFNC family in which at least one individual had an onset of seizures during the first week of life, a hallmark of the BFNC disorder. The results of the present study suggest the possibility that KCNQ2 mutation exist in patients with BFIC diagnosis. G812T of KCNQ2 gene is a novel mutation found in BFIC and functional expression of KCNQ2 G812T is required for understanding the mechanism of BFIC and other idiopathic epilepsy.
authors.affiliation: Department of Pediatrics, First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Xi-hui
authors.initials: XH
authors.lastname: Zhou
authors.forename: Ai-qun
authors.initials: AQ
authors.lastname: Ma
authors.forename: Xiao-hong
authors.initials: XH
authors.lastname: Liu
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.forename: Yan-min
authors.initials: YM
authors.lastname: Zhang
authors.forename: Rui-ming
authors.initials: RM
authors.lastname: Shi
mesh_terms: D000328:Adult; D017668:Age of Onset; D044466:Asian People; D004252:DNA Mutational Analysis; D020936:Epilepsy, Benign Neonatal / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D051658:KCNQ2 Potassium Channel / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012640:Seizures / Q000235:genetics* / Q000503:physiopathology
chemical_list: D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human