A novel mutation of the nicotinic acetylcholine receptor gene CHRNA4 in sporadic nocturnal frontal lobe epilepsy

Summary Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is known to be partly caused by mutations in the transmembrane domain (TM) 1-3 of the genes of the neuronal nicotinic acetylcholine receptor (nAChR) α4-subunit ( CHRNA4 ), β2-subunit ( CHRNB2 ) and α2-subunit ( CHRNA2 ). The more common cases of sporadic nocturnal frontal lobe epilepsy (NFLE) that are not differentiated from ADNFLE by phenotype have been found to be associated with the mutation of CHRNA4 reported in ADNFLE. In order to assess the genetic defects in NFLE, we performed a mutation screening in 33 unrelated patients with sporadic NFLE by amplifying and sequencing bidirectionally TM 1-3 of CHRNA4 , CHRNB2 and CHRNA2 which contain the mutations reported in ADNFLE. In screening CHRNA4 , we identified a novel mutation in one patient that causes a α4-R308H amino acid exchange outside the TM, and in the second intracellular loop between the third and fourth transmembrane domains. The mutation was not observed in 400 control chromosomes. No mutations were present in parts of CHRNB2 and CHRNA2 .