Pleiotropic functional effects of the first epilepsy-associated mutation in the human CHRNA2 gene.
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.
Hoda
Jean-Charles
JC
Department of Neuroscience, Medical Faculty, Geneva, Switzerland.
Wanischeck
Mario
M
Bertrand
Daniel
D
Steinlein
Ortrud K
OK
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
C436489:CHRNA2 protein, human; D011978:Receptors, Nicotinic