title: A Kv4.2 truncation mutation in a patient with temporal lobe epilepsy.
abstract: 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 Kv4.2 truncation mutation. Kv4.2 channels, encoded by the KCND2 gene, mediate A currents in the brain. The identified mutation corresponds to an N587fsX1 amino acid change, predicted to produce a truncated Kv4.2 protein lacking the last 44 amino acids in the carboxyl terminal. Electrophysiological analysis indicates attenuated K+ current density in cells expressing this Kv4.2-N587fsX1 mutant channel, which is consistent with a model of aberrant neuronal excitability characteristic of TLE. Our observations, together with other lines of evidence, raise the intriguing possibility of a role for KCND2 in the etiology of TLE.
authors.affiliation: Laboratory for Neurogenetics, RIKEN Brain Science Institute, Saitama 351-0198, Japan.
authors.forename: Baljinder
authors.initials: B
authors.lastname: Singh
authors.forename: Ikuo
authors.initials: I
authors.lastname: Ogiwara
authors.forename: Makoto
authors.initials: M
authors.lastname: Kaneda
authors.forename: Natsuko
authors.initials: N
authors.lastname: Tokonami
authors.forename: Emi
authors.initials: E
authors.lastname: Mazaki
authors.forename: Koichi
authors.initials: K
authors.lastname: Baba
authors.forename: Kazumi
authors.initials: K
authors.lastname: Matsuda
authors.forename: Yushi
authors.initials: Y
authors.lastname: Inoue
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamakawa
mesh_terms: D000200:Action Potentials / Q000235:genetics; D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics*; D002460:Cell Line; D004252:DNA Mutational Analysis; D004833:Epilepsy, Temporal Lobe / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D018408:Patch-Clamp Techniques; D010375:Pedigree; D011188:Potassium / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D051672:Shal Potassium Channels / Q000737:chemistry / Q000235:genetics*; D009435:Synaptic Transmission / Q000235:genetics
chemical_list: D051672:Shal Potassium Channels; D011188:Potassium