Journal article

Human nocturnal frontal lobe epilepsy: Pharmocogenomic profiles of pathogenic nicotinic acetylcholine receptor beta-subunit mutations outside the ion channel pore

Jean-Charles Hoda, Wenli Gu, Marc Friedli, Hilary A Phillips, Sonia Bertrand, Stylianos E Antonarakis, David Goudie, Richard Roberts, Ingrid E Scheffer, Carla Marini, Jayesh Patel, Samuel F Berkovic, John C Mulley, Ortrud K Steinlein, Daniel Bertrand

Molecular Pharmacology | AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS | Published : 2008

Abstract

Certain mutations in specific parts of the neuronal nicotinic acetylcholine receptor (nAChR) subunit genes CHRNA4, CHRNB2, and probably CHRNA2, can cause autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). All but one of the known causative mutations are located in the second transmembrane region (TM2), which serves as the major ion poreforming domain of the receptor. Functional characterization of these ADNFLE mutations has shown that although each mutant exhibits specific properties, they all confer a gain of function with increased sensitivity to acetylcholine. In this work, we characterize the second and third ADNFLE-associated mutations that are external to TM2 but affect diffe..

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