title: Pleiotropic functional effects of the first epilepsy-associated mutation in the human CHRNA2 gene.
abstract: Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) can be caused by mutations in the neuronal nicotinic acetylcholine receptor (nAChR) subunit genes CHRNA4 and CHRNB2. Recently, a point mutation (alpha2-I279N) associated with sleep-related epilepsy has been described in a third nAChR gene, CHRNA2. We demonstrate here that alpha2-I279N can be co-expressed with the major structural subunit CHRNB2. alpha2-I279N causes a marked gain-of-function effect and displays a distinct biopharmacological profile, including markedly reduced inhibition by carbamazepine and increased nicotine sensitivity.
authors.affiliation: Department of Neuroscience, Medical Faculty, Geneva, Switzerland.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Hoda
authors.forename: Mario
authors.initials: M
authors.lastname: Wanischeck
authors.forename: Daniel
authors.initials: D
authors.lastname: Bertrand
authors.forename: Ortrud K
authors.initials: OK
authors.lastname: Steinlein
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D017034:Epilepsy, Frontal Lobe / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics* / Q000378:metabolism; D014981:Xenopus
chemical_list: C436489:CHRNA2 protein, human; D011978:Receptors, Nicotinic