title: First mutation in the voltage-gated Nav1.1 subunit gene SCN1A with co-occurring familial hemiplegic migraine and epilepsy.
abstract: Almost all mutations in the SCN1A gene, encoding the alpha(1) subunit of neuronal voltage-gated Na(V)1.1 sodium channels, are associated with severe childhood epilepsy. Recently, two mutations were identified in patients with pure familial hemiplegic migraine (FHM). Here, we identified a novel SCN1A L263V mutation in a Portuguese family with partly co-segregating hemiplegic migraine and epilepsy. The L263V mutation segregated in five FHM patients, three of whom also had epileptic attacks, occurring independently from their hemiplegic migraine attacks. L263V is the first SCN1A mutation associated with FHM and co-occurring epilepsy in multiple mutation carriers, and is the clearest molecular link between migraine and epilepsy thus far. The results extend the clinical spectrum associated with SCN1A mutations and further strengthen the molecular evidence that FHM and epilepsy share, at least in part, similar molecular pathways.
authors.affiliation: Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
authors.forename: M-J
authors.initials: MJ
authors.lastname: Castro
authors.forename: A H
authors.initials: AH
authors.lastname: Stam
authors.forename: C
authors.initials: C
authors.lastname: Lemos
authors.forename: B
authors.initials: B
authors.lastname: de Vries
authors.forename: K R J
authors.initials: KR
authors.lastname: Vanmolkot
authors.forename: J
authors.initials: J
authors.lastname: Barros
authors.forename: G M
authors.initials: GM
authors.lastname: Terwindt
authors.forename: R R
authors.initials: RR
authors.lastname: Frants
authors.forename: J
authors.initials: J
authors.lastname: Sequeiros
authors.forename: M D
authors.initials: MD
authors.lastname: Ferrari
authors.forename: J M
authors.initials: JM
authors.lastname: Pereira-Monteiro
authors.forename: A M J M
authors.initials: AM
authors.lastname: van den Maagdenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000595:Amino Acid Sequence; D000818:Animals; D002648:Child; D004827:Epilepsy / Q000150:complications* / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020325:Migraine with Aura / Q000150:complications* / Q000235:genetics*; D009154:Mutation; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; 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