title: Novel SCN1A mutation in a proband with malignant migrating partial seizures of infancy.
abstract: OBJECTIVE
  To characterize a novel SCN1A mutation in a proband with malignant migrating partial seizures of infancy.
  
  
  METHODS
  Genomic DNA was isolated from blood and submitted for commercial testing. The identified missense mutation was confirmed in brain DNA obtained at autopsy. Genomic DNA from the brain of the proband was analyzed by comparative genome hybridization, and the coding exons of SCN9A were amplified. Quantitation studies of the mutant transcript were performed.
  
  
  METHODS
  Children's National Medical Center and Yale University School of Medicine. PROBAND: A full-term female infant who experienced seizure onset at age 10 weeks, with progression of hemiclonic, apneic, and multifocal migrating partial seizures leading to recurrent status epilepticus and death at age 9 months.
  
  
  METHODS
  Electroencephalographic and magnetic resonance imaging results, quantitative RNA expression, and secondary mutation test results.
  
  
  RESULTS
  The heterozygous missense mutation c.C5006C>A was identified by sequencing genomic DNA from blood and was confirmed in brain DNA. The resulting amino acid substitution p.A1669E alters an evolutionarily conserved residue in an intracellular linker of domain 4 of the SCN1A sodium channel protein Na(v)1.1. The mutant transcript is found to be expressed at levels comparable to the wild-type allele in brain RNA. No variation in copy number was detected in the chromosome region 2q24 containing SCN1A or elsewhere in the genome. No mutations were detected in the linked sodium channel gene SCN9A, which has been reported to act as a modifier of SCN1A mutations.
  
  
  CONCLUSIONS
  This report expands the spectrum of SCN1A epileptic channelopathies to include malignant migrating partial seizures of infancy.
authors.affiliation: Department of Neurology, Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010-2970, USA.
authors.forename: Emily R
authors.initials: ER
authors.lastname: Freilich
authors.forename: Julie M
authors.initials: JM
authors.lastname: Jones
authors.forename: William D
authors.initials: WD
authors.lastname: Gaillard
authors.forename: Joan A
authors.initials: JA
authors.lastname: Conry
authors.forename: Tammy N
authors.initials: TN
authors.lastname: Tsuchida
authors.forename: Christine
authors.initials: C
authors.lastname: Reyes
authors.forename: Sulayman
authors.initials: S
authors.lastname: Dib-Hajj
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Waxman
authors.forename: Miriam H
authors.initials: MH
authors.lastname: Meisler
authors.forename: Phillip L
authors.initials: PL
authors.lastname: Pearl
mesh_terms: D000409:Alanine; D019943:Amino Acid Substitution; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D004569:Electroencephalography; D004828:Epilepsies, Partial / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D018698:Glutamic Acid; D006801:Humans; D007223:Infant; D007621:Karyotyping; D008279:Magnetic Resonance Imaging; D020125:Mutation, Missense; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D015222:Sodium Channels / Q000235:genetics*; D013226:Status Epilepticus / Q000235:genetics / Q000503:physiopathology
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels; D018698:Glutamic Acid; D000409:Alanine