title: De novo SCN1A mutations in migrating partial seizures of infancy.
abstract: OBJECTIVE
  To determine the genetic etiology of the severe early infantile onset syndrome of malignant migrating partial seizures of infancy (MPSI).
  
  
  METHODS
  Fifteen unrelated children with MPSI were screened for mutations in genes associated with infantile epileptic encephalopathies: SCN1A, CDKL5, STXBP1, PCDH19, and POLG. Microarray studies were performed to identify copy number variations.
  
  
  RESULTS
  One patient had a de novo SCN1A missense mutation p.R862G that affects the voltage sensor segment of SCN1A. A second patient had a de novo 11.06 Mb deletion of chromosome 2q24.2q31.1 encompassing more than 40 genes that included SCN1A. Screening of CDKL5 (13/15 patients), STXBP1 (13/15), PCDH19 (9/11 females), and the 3 common European mutations of POLG (11/15) was negative. Pathogenic copy number variations were not detected in 11/12 cases.
  
  
  CONCLUSIONS
  Epilepsies associated with SCN1A mutations range in severity from febrile seizures to severe epileptic encephalopathies including Dravet syndrome and severe infantile multifocal epilepsy. MPSI is now the most severe SCN1A phenotype described to date. While not a common cause of MPSI, SCN1A screening should now be considered in patients with this devastating epileptic encephalopathy.
authors.affiliation: Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Carranza Rojo
authors.forename: L
authors.initials: L
authors.lastname: Hamiwka
authors.forename: J M
authors.initials: JM
authors.lastname: McMahon
authors.forename: L M
authors.initials: LM
authors.lastname: Dibbens
authors.forename: T
authors.initials: T
authors.lastname: Arsov
authors.forename: A
authors.initials: A
authors.lastname: Suls
authors.forename: T
authors.initials: T
authors.lastname: Stödberg
authors.forename: K
authors.initials: K
authors.lastname: Kelley
authors.forename: E
authors.initials: E
authors.lastname: Wirrell
authors.forename: B
authors.initials: B
authors.lastname: Appleton
authors.forename: M
authors.initials: M
authors.lastname: Mackay
authors.forename: J L
authors.initials: JL
authors.lastname: Freeman
authors.forename: S C
authors.initials: SC
authors.lastname: Yendle
authors.forename: S F
authors.initials: SF
authors.lastname: Berkovic
authors.forename: T
authors.initials: T
authors.lastname: Bienvenu
authors.forename: P
authors.initials: P
authors.lastname: De Jonghe
authors.forename: D R
authors.initials: DR
authors.lastname: Thorburn
authors.forename: J C
authors.initials: JC
authors.lastname: Mulley
authors.forename: H C
authors.initials: HC
authors.lastname: Mefford
authors.forename: I E
authors.initials: IE
authors.lastname: Scheffer
mesh_terms: D015820:Cadherins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D056915:DNA Copy Number Variations / Q000235:genetics*; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D004828:Epilepsies, Partial / Q000150:complications / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D007223:Infant; D008297:Male; D051938:Munc18 Proteins / Q000235:genetics; D009154:Mutation; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D000091363:Protocadherins; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D015820:Cadherins; D051938:Munc18 Proteins; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C438605:PCDH19 protein, human; D000091363:Protocadherins; C568242:SCN1A protein, human; C497937:STXBP1 protein, human; D015222:Sodium Channels; D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human