title: Cryptogenic epileptic syndromes related to SCN1A: twelve novel mutations identified.
abstract: BACKGROUND
  Sodium channel alpha 1 subunit gene, SCN1A, is the gene encoding the neuronal voltage-gated sodium channel alpha 1 subunit (Na(v)1.1) and is mutated in different forms of epilepsy. Mutations in this gene were observed in more than 70% of patients with severe myoclonic epilepsy of infancy (SMEI) and were also found in different types of infantile epileptic encephalopathy.
  
  
  OBJECTIVE
  To search for disease-causing mutations in SCN1A in patients with cryptogenic epileptic syndromes (ie, syndromes with an unknown cause).
  
  
  METHODS
  Clinical characterization and molecular genetic analysis of a cohort of patients.
  
  
  METHODS
  University hospitals, rehabilitation centers, and molecular biology laboratories.
  
  
  METHODS
  Sixty unrelated patients with cryptogenic epileptic syndromes.
  
  
  METHODS
  Samples of DNA were analyzed for mutations and for large heterozygous deletions encompassing the SCN1A gene. A search for microdeletions in the SCN1A gene was also performed in the subset of patients with SMEI/SMEI-borderland who had negative results at the point mutation screening.
  
  
  RESULTS
  No large deletions at the SCN1A locus were found in any of the patients analyzed. In contrast, 13 different point mutations were identified in 12 patients: 10 with SMEI, 1 with generalized epilepsy with febrile seizures plus, and 1 with cryptogenic focal epilepsy. An additional search for SCN1A intragenic microdeletions in the remaining patients with SMEI/SMEI-borderland and no point mutations was also negative.
  
  
  CONCLUSIONS
  These results confirm the role of the SCN1A gene in different types of epilepsy, including cryptogenic epileptic syndromes. However, large deletions encompassing SCN1A were not common disease-causing rearrangements in this group of epilepsies.
authors.affiliation: Clinical Neurophysiology Unit, E. Medea Scientific Institute, Lecco, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Zucca
authors.forename: Francesca
authors.initials: F
authors.lastname: Redaelli
authors.forename: Roberta
authors.initials: R
authors.lastname: Epifanio
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Zanotta
authors.forename: Antonino
authors.initials: A
authors.lastname: Romeo
authors.forename: Monica
authors.initials: M
authors.lastname: Lodi
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Veggiotti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Airoldi
authors.forename: Chris
authors.initials: C
authors.lastname: Panzeri
authors.forename: Romina
authors.initials: R
authors.lastname: Romaniello
authors.forename: Gianni
authors.initials: G
authors.lastname: De Polo
authors.forename: Paolo
authors.initials: P
authors.lastname: Bonanni
authors.forename: Simonetta
authors.initials: S
authors.lastname: Cardinali
authors.forename: Cinzia
authors.initials: C
authors.lastname: Baschirotto
authors.forename: Loreto
authors.initials: L
authors.lastname: Martorell
authors.forename: Renato
authors.initials: R
authors.lastname: Borgatti
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Bassi
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D004252:DNA Mutational Analysis; D004831:Epilepsies, Myoclonic / Q000175:diagnosis / Q000235:genetics; D004828:Epilepsies, Partial / Q000175:diagnosis / Q000235:genetics; D004827:Epilepsy / Q000175:diagnosis / Q000235:genetics*; D004829:Epilepsy, Generalized / Q000175:diagnosis / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006580:Genetic Carrier Screening; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation; D003294:Seizures, Febrile / Q000175:diagnosis / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels