1. Augmented currents of an HCN2 variant in patients with febrile seizure syndromes.
- Author
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Dibbens LM, Reid CA, Hodgson B, Thomas EA, Phillips AM, Gazina E, Cromer BA, Clarke AL, Baram TZ, Scheffer IE, Berkovic SF, and Petrou S
- Subjects
- Animals, Biophysics methods, Cyclic AMP pharmacology, Cyclic Nucleotide-Gated Cation Channels genetics, DNA Mutational Analysis methods, Electric Stimulation methods, Gene Frequency, Humans, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Membrane Potentials drug effects, Membrane Potentials genetics, Oocytes, Patch-Clamp Techniques methods, Potassium Channels genetics, Proline genetics, Transfection methods, Xenopus, Ion Channels genetics, Seizures, Febrile genetics, Sequence Deletion genetics
- Abstract
The genetic architecture of common epilepsies is largely unknown. HCNs are excellent epilepsy candidate genes because of their fundamental neurophysiological roles. Screening in subjects with febrile seizures and genetic epilepsy with febrile seizures plus revealed that 2.4% carried a common triple proline deletion (delPPP) in HCN2 that was seen in only 0.2% of blood bank controls. Currents generated by mutant HCN2 channels were approximately 35% larger than those of controls; an effect revealed using automated electrophysiology and an appropriately powered sample size. This is the first association of HCN2 and familial epilepsy, demonstrating gain of function of HCN2 current as a potential contributor to polygenic epilepsy.
- Published
- 2010
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