PubMed 24639406

Title: A novel KCNA1 mutation causing episodic ataxia type I.

Authors: Saskia Lassche, Sergio Lainez, Bastiaan R Bloem, Bart P C van de Warrenburg, Jeannette Hofmeijer, Henny H Lemmink, Joost G J Hoenderop, René J M Bindels, Gea Drost

Journal, date & volume: Muscle Nerve, 2014 Mar 18 , ,

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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.