title: A KCNQ2 E515D mutation associated with benign familial neonatal seizures and continuous spike and waves during slow-wave sleep syndrome in Taiwan.
abstract: OBJECTIVE
  Pediatric epilepsy caused by a KCNQ2 gene mutation usually manifests as benign familial neonatal seizures (BFNS) during the 1stweek of life. However, the exact mechanism, phenotype, and genotype of the KCNQ2 mutation are unclear.
  
  
  METHODS
  We studied the KCNQ2 genotype from 75 nonconsanguineous patients with childhood epilepsy without an identified cause (age range: from 2 days to 18 years) and from 55 healthy adult controls without epilepsy. KCNQ2 mutation variants were transfected into HEK293 cells to investigate what functional changes they induced.
  
  
  RESULTS
  Four (5%) of the patients had the E515D KCNQ2 mutation, which the computer-based PolyPhen algorithm predicted to be deleterious. Their seizure outcomes were favorable, but three had an intellectual disability. Two patients with E515D presented with continuous spikes and waves during slow-wave sleep (CSWS), and the other two presented with BFNS. We also analyzed 10 affected family members with the same KCNQ2 mutation: all had epilepsy (8 had BFNS and 2 had CSWS). A functional analysis showed that the recordings of the E515D currents were significantly different (p<0.05), which suggested that channels with KCNQ2 E515D variants are less sensitive to voltage and require stronger depolarization to reach opening probabilities than those with the wild type or N780T (a benign polymorphism).
  
  
  CONCLUSIONS
  KCNQ2 mutations can cause various phenotypes in children: they lead to BFNS and CSWS. We hypothesize that patients with the KCNQ2 E515D mutation are susceptible to seizures.
authors.affiliation: Division of Pediatric Neurology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan; Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan. Electronic address: y610@mercury.csmu.edu.tw.
authors.forename: Inn-Chi
authors.initials: IC
authors.lastname: Lee
authors.affiliation: Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Genetics Laboratory and Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Jiann-Jou
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Genetics Laboratory and Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan. Electronic address: i0000528@ms12.hinet.net.
authors.forename: Shuan-Yow
authors.initials: SY
authors.lastname: Li
mesh_terms: D000293:Adolescent; D002648:Child; D004569:Electroencephalography; D020936:Epilepsy, Benign Neonatal / Q000235:genetics* / Q000503:physiopathology; D057809:HEK293 Cells; D006801:Humans; D007223:Infant; D051658:KCNQ2 Potassium Channel / Q000235:genetics*; D009154:Mutation; D012890:Sleep / Q000502:physiology*
chemical_list: D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human
keywords: E515D mutation; KCNQ2; benign familial neonatal seizures; continuous spikes and waves during slow-wave sleep