title: Independent occurrence of the CHRNA4 Ser248Phe mutation in a Norwegian family with nocturnal frontal lobe epilepsy.
abstract: OBJECTIVE
  To describe the clinical features of a family from Northern Norway in which autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is associated with a Ser248Phe amino acid exchange in the second transmembrane domain of the neuronal nicotinic acetylcholine receptor alpha4 subunit (CHRNA4). We also tested for evidence of a de novo mutation or founder effect by comparing haplotypes with the original Australian family where the Ser248Phe mutation was first described.
  
  
  METHODS
  Clinical details were obtained from 19 family members. Personal interviews and genetic analysis were carried out in 17. Parts of the coding region of CHRNA4 were sequenced, and two known polymorphisms (bp555/FokI, bp594/CfoI) were typed by restriction analysis.
  
  
  RESULTS
  Eleven individuals had ADNFLE. The haplotypes of the mutation-carrying alleles of affected individuals from the Northern Norwegian and the Australian ADNFLE family are different. The phenotypic expressions are remarkably similar.
  
  
  CONCLUSIONS
  The Ser248Phe mutation occurred independently in both families. Given the rarity of the disease, this suggests that not only the position of a mutation in the coding sequence but also the type of an amino acid exchange is important for the etiology of ADNFLE. The phenotypic similarity of these two families with different genetic backgrounds suggests that the Ser248Phe mutation largely determines the phenotype, with relatively little influence of other background genes.
authors.affiliation: Institute for Human Genetics, Friedrich-Wilhelms-University of Bonn, Bonn, Germany. osteinl@mailer.meb.uni-bonn.de
authors.forename: O K
authors.initials: OK
authors.lastname: Steinlein
authors.forename: J
authors.initials: J
authors.lastname: Stoodt
authors.forename: J
authors.initials: J
authors.lastname: Mulley
authors.forename: S
authors.initials: S
authors.lastname: Berkovic
authors.forename: I E
authors.initials: IE
authors.lastname: Scheffer
authors.forename: E
authors.initials: E
authors.lastname: Brodtkorb
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001315:Australia / Q000453:epidemiology; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D017034:Epilepsy, Frontal Lobe / Q000453:epidemiology / Q000235:genetics*; D005190:Family; D005260:Female; D018703:Founder Effect; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009664:Norway / Q000453:epidemiology; D010375:Pedigree; D010641:Phenotype; D011110:Polymorphism, Genetic; D011978:Receptors, Nicotinic / Q000235:genetics*; D020539:Sequence Analysis, Protein
chemical_list: D011978:Receptors, Nicotinic