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 Kv1.1I262M mutant DNA were transfected transiently in HEK293 cells to evaluate the influence of the mutation. We found that Kv1.1I262M 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. Muscle Nerve 50:289–291, 2014