title: Neuronal nicotinic receptors in human epilepsy.
abstract: Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a rare monogenic idiopathic partial epilepsy characterized by clusters of frontal lobe motor seizures during sleep. Recently, it has been shown that mutations of the chromosome-20q-located neuronal nicotinic acetylcholine receptor alpha4-subunit (CHRNA4) are associated with ADNFLE in some families, but that other families are not linked to this locus. Both CHRNA4 mutations (Ser248Phe and 776ins3) identified so far are found in the pore-forming second transmembrane region of the gene. Electrophysiological studies showed that mutations in this functional important part of the receptor subunit have a profound effect on the permeability for calcium ions. Interestingly, the Ser248Phe mutation was found again in a second ADNFLE family. Haplotype analysis excluded a founder effect and showed that Ser248Phe occurred independently twice. This provides the possibility to study the effect of the same mutation on different genetic backgrounds. Several attempts have been made to identify additional genes responsible for ADNFLE. But despite some positive linkage results including the CHRNA3-CHRNA5-CHRNB2 cluster on chromosome 15q24, no further mutations have been found so far. The mutation screening of functionally important parts of CHRNA5 in 12 ADNFLE patients did not support a causative role of this nicotinic acetylcholine receptor subunit.
authors.affiliation: Institute for Human Genetics, RFW University of Bonn, Wilhelmstrasse 31, Bonn, Germany. osteinl@mailer.meb.uni-bonn.de
authors.forename: O K
authors.initials: OK
authors.lastname: Steinlein
mesh_terms: D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D002890:Chromosomes, Human, Pair 20; D017034:Epilepsy, Frontal Lobe / Q000235:genetics* / Q000378:metabolism; D005091:Exons / Q000235:genetics; D020180:Heteroduplex Analysis; D006801:Humans; D007438:Introns / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D010641:Phenotype; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*
chemical_list: D011978:Receptors, Nicotinic