title: A missense mutation in the neuronal nicotinic acetylcholine receptor alpha 4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy.
abstract: Epilepsy affects at least 2% of the population at some time in their lives. The epilepsies are a heterogeneous group of disorders, many with an inherited component. Although specific genes have been identified in a few rare diseases causing seizures as part of a more diffuse brain disorder, the molecular pathology of the common idiopathic epilepsies is still unknown. Linkage has been reported for some generalised epilepsy syndromes, but only very recently for familial partial epilepsy syndromes. Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a partial epilepsy causing frequent, violent, brief seizures at night, usually beginning in childhood. The gene for ADNFLE maps to chromosome 20q13.2-q13.3 in one large Australian kindred. The neuronal nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4) maps to the same region of 20q (ref. 12) and the gene is expressed in all layers of the frontal cortex. We screened affected family members for mutations within CHRNA4 and found a missense mutation that replaces serine with phenylalanine at codon 248, a strongly conserved amino acid residue in the second transmembrane domain. The mutation is present in all 21 available affected family members and in four obligate carriers, but not in 333 healthy control subjects.
authors.affiliation: Institute of Human Genetics, University of Bonn, Germany.
authors.forename: O K
authors.initials: OK
authors.lastname: Steinlein
authors.forename: J C
authors.initials: JC
authors.lastname: Mulley
authors.forename: P
authors.initials: P
authors.lastname: Propping
authors.forename: R H
authors.initials: RH
authors.lastname: Wallace
authors.forename: H A
authors.initials: HA
authors.lastname: Phillips
authors.forename: G R
authors.initials: GR
authors.lastname: Sutherland
authors.forename: I E
authors.initials: IE
authors.lastname: Scheffer
authors.forename: S F
authors.initials: SF
authors.lastname: Berkovic
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002645:Chickens; D002874:Chromosome Mapping; D002890:Chromosomes, Human, Pair 20; D017931:DNA Primers; D017034:Epilepsy, Frontal Lobe / Q000235:genetics*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D051381:Rats; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: D017931:DNA Primers; D011978:Receptors, Nicotinic