title: A new locus for autosomal dominant nocturnal frontal lobe epilepsy maps to chromosome 1.
abstract: BACKGROUND
  Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is caused by mutations in the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (CHRNA4) gene, mapping on chromosome 20q13.2. A second ADNFLE locus was mapped on chromosome 15q24.
  
  
  OBJECTIVE
  To report a new third ADNFLE locus on chromosome 1 in a large Italian family.
  
  
  METHODS
  The authors performed a clinical and genetic study in a large, three-generation ADNFLE family from southern Italy, including eight affected individuals and three obligate carriers.
  
  
  RESULTS
  The age at onset of seizures was around 9 years of age and all affected individuals manifested nocturnal partial seizures of frontal lobe origin. Interictal awake and sleep EEG recordings showed no definite epileptiform abnormalities in most patients. Ictal video-EEG showed that the attacks were partial seizures with a frontal lobe semiology. Intellectual and neurologic examinations, and brain CT or MRI results were always normal. Carbamazepine was effective in all treated patients. Exclusion mapping of the known loci linked to ADNFLE-ENFL1, and ENFL2, on chromosomes 20q13.2 and 15q24-was performed on the pedigree before starting the genome-wide linkage analysis. The whole genome scan mapping allowed the identification of a new ADNFLE locus spanning the pericentromeric region of chromosome 1.
  
  
  CONCLUSIONS
  The authors provided evidence for a third locus associated to autosomal dominant nocturnal frontal lobe epilepsy on chromosome 1. Among the known genes mapping within this critical region, the ss2 subunit of the nicotinic receptor (CHRNB2) represents the most obvious candidate.
authors.affiliation: Institute of Neurology, School of Medicine, Catanzaro, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Gambardella
authors.forename: G
authors.initials: G
authors.lastname: Annesi
authors.forename: M
authors.initials: M
authors.lastname: De Fusco
authors.forename: A
authors.initials: A
authors.lastname: Patrignani
authors.forename: U
authors.initials: U
authors.lastname: Aguglia
authors.forename: F
authors.initials: F
authors.lastname: Annesi
authors.forename: A A
authors.initials: AA
authors.lastname: Pasqua
authors.forename: P
authors.initials: P
authors.lastname: Spadafora
authors.forename: R L
authors.initials: RL
authors.lastname: Oliveri
authors.forename: P
authors.initials: P
authors.lastname: Valentino
authors.forename: M
authors.initials: M
authors.lastname: Zappia
authors.forename: A
authors.initials: A
authors.lastname: Ballabio
authors.forename: G
authors.initials: G
authors.lastname: Casari
authors.forename: A
authors.initials: A
authors.lastname: Quattrone
mesh_terms: D000293:Adolescent; D000328:Adult; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D017034:Epilepsy, Frontal Lobe / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D008297:Male; D010375:Pedigree