A KV4.2 truncation mutation in a patient with temporal lobe epilepsy

Temporal lobe epilepsy (TLE) has a multifactorial etiology involving developmental, environmental, and genetic components. Here, we report a voltage-gated potassium channel gene mutation found in a TLE patient, namely a K(v)4.2 truncation mutation. K(v)4.2 channels, encoded by the A'CND2 gene, mediate A currents in the brain. The identified mutation corresponds to an N587fsX1 amino acid change, predicted to produce a truncated K(v)4.2 protein lacking the last 44 amino acids in the carboxyl terminal. Electrophysiological analysis indicates attenuated K+ current density in cells expressing this K(v)4.2-N587fsX1 mutantchannel, which is consistent with a model ofaberrant neuronal excitabilit, * v characteristic of TLE. Our observations, together with other lines ofevidence, raise the intriguing possibility of a role for KCjVD2 in the etiology of TLE. (c) 2006 Elsevier Inc. All rights reserved.