title: KCNQ2-Associated Neonatal Epilepsy: Phenotype Might Correlate With Genotype.
abstract: We analyzed the KCNQ2 wild-type gene and 3 mutations to highlight the important association between the KCNQ2 phenotype and genotype. The clinical phenotypes of 3 mutations (p.E515D, p.V543 M, and p.R213Q) were compared. KCNQ2, wild-type, and mutant KCNQ2 alleles were transfected into HEK293 cells before whole-cell patch-clamp analysis. Neurodevelopmental outcomes were worst in patients with the p.R213Q mutation, better in patients with the p.E515D mutation, and best in patients with the novel p.V543 M mutation. The currents in p.E515D and in p.V543 M were significantly lower than in the wild type in homomeric and heteromeric transfected HEK293 cells ( P < .05). The opening threshold shifted to values that were more positive, and the maximal current induced by strong depolarization was higher in cells with the p.E515D and p.R213Q mutations. We provide evidence that genotype is involved in determining clinical phenotype, including the seizure frequency and outcome.
authors.affiliation: 1 Division of Pediatric Neurology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan.|2 Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Inn-Chi
authors.initials: IC
authors.lastname: Lee
authors.affiliation: 3 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: 4 Department of Pediatrics, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
authors.forename: Jao-Shwann
authors.initials: JS
authors.lastname: Liang
authors.affiliation: 5 Division of Pediatric Neurology, Changhua Christian Children's Hospital, Changhua, Taiwan.
authors.forename: Tung-Ming
authors.initials: TM
authors.lastname: Chang
authors.affiliation: 2 Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.|3 Genetics Laboratory and Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Shuan-Yow
authors.initials: SY
authors.lastname: Li
mesh_terms: D002648:Child; D004827:Epilepsy / Q000235:genetics*; D005192:Family Health; D005260:Female; D005838:Genotype; D057809:HEK293 Cells; D006801:Humans; D007223:Infant; D051659:KCNQ3 Potassium Channel / Q000235:genetics*; D008297:Male; D008564:Membrane Potentials / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D018408:Patch-Clamp Techniques; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014162:Transfection
chemical_list: D051659:KCNQ3 Potassium Channel
keywords: KCNQ2; functional study; neonatal epilepsy; outcome; phenotype