title: De novo SCN1A mutations are a major cause of severe myoclonic epilepsy of infancy.
abstract: Severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome) is a rare disorder occurring in young children often without a family history of a similar disorder. The earliest disease manifestations are usually fever-associated seizures. Later in life, patients display different types of afebrile seizures including myoclonic seizures. Arrest of psychomotor development occurs in the second year of life and most patients become ataxic. Patients are resistant to antiepileptic drug therapy. Recently, we described de novo mutations of the neuronal sodium channel alpha-subunit gene SCN1A in seven isolated SMEI patients. To investigate the contribution of SCN1A mutations to the etiology of SMEI, we examined nine additional SMEI patients. We observed eight coding and one noncoding mutation. In contrast to our previous study, most mutations are missense mutations clustering in the S4-S6 region of SCN1A. These findings demonstrate that de novo mutations in SCN1A are a major cause of isolated SMEI.
authors.affiliation: Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), Born-Bunge Foundation, University of Antwerp (UIA), Antwerpen, Belgium.
authors.forename: Lieve
authors.initials: L
authors.lastname: Claes
authors.forename: Berten
authors.initials: B
authors.lastname: Ceulemans
authors.forename: Dominique
authors.initials: D
authors.lastname: Audenaert
authors.forename: Katrien
authors.initials: K
authors.lastname: Smets
authors.forename: Ann
authors.initials: A
authors.lastname: Löfgren
authors.forename: Jurgen
authors.initials: J
authors.lastname: Del-Favero
authors.forename: Sirpa
authors.initials: S
authors.lastname: Ala-Mello
authors.forename: Lina
authors.initials: L
authors.lastname: Basel-Vanagaite
authors.forename: Barbara
authors.initials: B
authors.lastname: Plecko
authors.forename: Salmo
authors.initials: S
authors.lastname: Raskin
authors.forename: Paul
authors.initials: P
authors.lastname: Thiry
authors.forename: Nicole I
authors.initials: NI
authors.lastname: Wolf
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
authors.forename: Peter
authors.initials: P
authors.lastname: De Jonghe
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D007438:Introns / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / 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