title: Autosomal dominant nocturnal frontal lobe epilepsy in a Spanish family with a Ser252Phe mutation in the CHRNA4 gene.
abstract: BACKGROUND
  A large family with autosomal dominant nocturnal frontal lobe epilepsy from the south of Spain was studied. The clinical appearance of the disease in this family, which included 28 members, of whom 11 were affected and 2 were obligate carriers, was identical to that previously described in an Australian family and a Norwegian family, in which mutations in exon 5 of the CHRNA4 gene were found.
  
  
  METHODS
  Following DNA extraction, the family was genotyped with 4 fluorescent markers flanking the locus to the CHRNA4 gene on chromosome 20q13.3, and lod score computations were performed. The exon 5 of the CHRNA4 gene was amplified between nucleotides 535 and 825 and polymerase chain reaction products were purified and sequenced directly.
  
  
  RESULTS
  The same missense mutation as that found in the Australian family, C-->T, which causes the replacement of a serine with phenylalanine in amino acid 252 in exon 5, was detected. This mutation segregated with the disorder in all 11 affected members, in the 2 obligate carriers, and in 1 asymptomatic sibling, and was not found in 1 spouse and 1 daughter. Neither of the 2 polymorphisms found in a series of families with epilepsy were found in our sample [corrected].
  
  
  CONCLUSIONS
  These data confirm the clinical homogeneity in the phenotypic expression of autosomal dominant nocturnal frontal lobe epilepsy caused by mutation in the CHRNA4 gene, and the pathogenic role of the Ser252Phe mutation in this disorder.
authors.affiliation: Experimental Unit, Hospital Nuestra Señora de Aránzazu, San Sebastián, Basque Country, Spain. uniexpe2@chdo.osakidetza.net
authors.forename: A
authors.initials: A
authors.lastname: Sáenz
authors.forename: J
authors.initials: J
authors.lastname: Galán
authors.forename: C
authors.initials: C
authors.lastname: Caloustian
authors.forename: F
authors.initials: F
authors.lastname: Lorenzo
authors.forename: C
authors.initials: C
authors.lastname: Márquez
authors.forename: N
authors.initials: N
authors.lastname: Rodríguez
authors.forename: M D
authors.initials: MD
authors.lastname: Jiménez
authors.forename: J J
authors.initials: JJ
authors.lastname: Poza
authors.forename: A M
authors.initials: AM
authors.lastname: Cobo
authors.forename: D
authors.initials: D
authors.lastname: Grid
authors.forename: J F
authors.initials: JF
authors.lastname: Prud'homme
authors.forename: A
authors.initials: A
authors.lastname: López de Munain
mesh_terms: D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D017034:Epilepsy, Frontal Lobe / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010649:Phenylalanine / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D011978:Receptors, Nicotinic / Q000235:genetics*; D012694:Serine / Q000235:genetics*; D013030:Spain
chemical_list: D010649:Phenylalanine; D011978:Receptors, Nicotinic; D012694:Serine