The CHRNB2 mutation I312M is associated with epilepsy and distinct memory deficits.
Mutations in nAChRs are found in a rare form of nocturnal frontal lobe epilepsy (ADNFLE). Previously, some nAChR mutations have been described that are associated with additional neurological features such as psychiatric disorders or cognitive defects. Here, we report a new CHRNB2 mutation located in transmembrane region 3 (M3), outside the known ADNFLE mutation cluster. The CHRNB2 mutation I312M, which occurred de novo in twins, markedly increases the receptor's sensitivity to acetylcholine. Phenotypically, the mutation is associated not only with typical ADNFLE, but also with distinct deficits in memory. The cognitive problems are most obvious in tasks requiring the organization and storage of verbal information.
Bertrand
Daniel
D
Department of Neurosciences, Medical Faculty, CMU, 1211 Geneva 4, Switzerland.
Elmslie
Frances
F
Hughes
Elaine
E
Trounce
John
J
Sander
Thomas
T
Bertrand
Sonia
S
Steinlein
Ortrud K
OK
D000109:Acetylcholine / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D003072:Cognition Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D004252:DNA Mutational Analysis; D004827:Epilepsy / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000503:physiopathology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011978:Receptors, Nicotinic / Q000235:genetics*; D009435:Synaptic Transmission / Q000235:genetics
D000109:Acetylcholine; D011978:Receptors, Nicotinic