Identification of a New Mutation Underlying Regressive Episodic Ataxia Type I.

Episodic ataxia type 1 (EA1), a -like K, is a consequence of genetic anomalies in the gene that lead to dysfunctions in the voltage-gated K channel Kv1. 1. Generally, mutations are inherited in an autosomal dominant manner. Here we report the clinical phenotype of an EA1 patient characterized by ataxia attacks that decrease in frequency with age, and eventually leading to therapy discontinuation. A new mutation (c.932G>A) that changed a highly conserved glycine residue into an aspartate (p.G311D) was identified by using targeted next-generation sequencing. The conserved glycine is located in the S4-S5 linker, a crucial domain controlling Kv1.1 channel gating. analyses predicted the mutation deleterious. Heterologous expression of the mutant (Kv1.1-G311D) channels resulted in remarkably decreased amplitudes of measured current, confirming the identified variant is pathogenic. Collectively, these findings corroborate the notion that EA1 also results from variants and point out that regardless of the mutation-induced deleterious loss of Kv1.1 channel function the ataxia phenotype may improve spontaneously.