title: A novel KCNA1 mutation causing episodic ataxia type I.
abstract: We describe the clinical phenotype of a novel de novo KNCA1 mutation, and functional characterization of the effects of the mutation on Kv1.1 channel function. HEK293 cells were transfected transiently with either wild-type or mutant channels. Representative currents were evoked after application of a series of square voltage steps from -80 mV to +50 mV in 200-ms intervals from Vh = -80 mV. Extracellular K(+) was added to evoke tail currents. Equal amounts of wild-type and Kv1.1(I262M) mutant DNA were transfected transiently in HEK293 cells to evaluate the influence of the mutation. We found that Kv1.1(I262M) leads to a defective voltage-gated potassium channel. Coexpression studies revealed a dominant-negative effect. We describe the phenotype of a novel KCNA1 mutation causing episodic ataxia. Patch-clamp studies confirm the pathogenicity of the mutation in vitro and suggest that it is dominant with respect to wild-type.
authors.affiliation: Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Saskia
authors.initials: S
authors.lastname: Lassche
authors.forename: Sergio
authors.initials: S
authors.lastname: Lainez
authors.forename: Bastiaan R
authors.initials: BR
authors.lastname: Bloem
authors.forename: Bart P C
authors.initials: BP
authors.lastname: van de Warrenburg
authors.forename: Jeannette
authors.initials: J
authors.lastname: Hofmeijer
authors.forename: Henny H
authors.initials: HH
authors.lastname: Lemmink
authors.forename: Joost G J
authors.initials: JG
authors.lastname: Hoenderop
authors.forename: René J M
authors.initials: RJ
authors.lastname: Bindels
authors.forename: Gea
authors.initials: G
authors.lastname: Drost
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D006801:Humans; D051662:Kv1.1 Potassium Channel / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D020754:Spinocerebellar Ataxias / Q000235:genetics*
chemical_list: C496946:KCNA1 protein, human; D051662:Kv1.1 Potassium Channel
keywords: KCNA1; channelopathy; episodic ataxia type 1; ion channels; potassium channel