title: Phenotypic comparison of two Scottish families with mutations in different genes causing autosomal dominant nocturnal frontal lobe epilepsy.
abstract: OBJECTIVE
  Mutations in genes coding for the alpha 4 and beta 2 subunits of the neuronal nicotinic acetylcholine receptor receptor (CHRN) are known to cause autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Here we examined the phenotypes in two families, from the same ethnic and geographic backgrounds, with ADNFLE as a result of mutations in these two different subunits of CHRN.
  
  
  METHODS
  All affected family members underwent a detailed clinical evaluation and review of available EEG, neuroimaging, and videotapes of seizures. The molecular study of family D is reported here; family S has a previously reported mutation in the beta 2 subunit of CHRN.
  
  
  RESULTS
  A total of 16 individuals with ADNFLE were identified in the two families. In both families, seizure semiology, age at seizure onset, and the natural history of the seizure disorder was similar. Intrafamilial variation in terms of severity of epilepsy syndrome was present in both families. A significant number of individuals from each family had a history of psychological problems. The molecular study of family D revealed a Ser248Phe mutation in the alpha 4 subunit of CHRN.
  
  
  CONCLUSIONS
  The epilepsy phenotype is not distinguishable in the two families who have ADNFLE as a result of mutations in genes coding for different CHRN subunits. This is likely to be due to the similar functional consequences of each mutation on the CHRN receptor.
authors.affiliation: Ninewells Hospital and Medical School, Dundee, Scotland. mclellanaisla@doctors.org.uk
authors.forename: Ailsa
authors.initials: A
authors.lastname: McLellan
authors.forename: Hilary A
authors.initials: HA
authors.lastname: Phillips
authors.forename: Christopher
authors.initials: C
authors.lastname: Rittey
authors.forename: Martin
authors.initials: M
authors.lastname: Kirkpatrick
authors.forename: John C
authors.initials: JC
authors.lastname: Mulley
authors.forename: David
authors.initials: D
authors.lastname: Goudie
authors.forename: John B P
authors.initials: JB
authors.lastname: Stephenson
authors.forename: John
authors.initials: J
authors.lastname: Tolmie
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Berkovic
authors.forename: Sameer M
authors.initials: SM
authors.lastname: Zuberi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002869:Chromosome Aberrations; D015897:Comorbidity; D004252:DNA Mutational Analysis; D017034:Epilepsy, Frontal Lobe / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005799:Genes, Dominant / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000175:diagnosis / Q000235:genetics; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D011978:Receptors, Nicotinic / Q000235:genetics*; D012606:Scotland
chemical_list: D005819:Genetic Markers; D011978:Receptors, Nicotinic