title: Novel mutation confirms seizure locus SCN1A is also familial hemiplegic migraine locus FHM3.
abstract: Although SCN1A, the gene encoding the neuronal voltage-gated sodium channel, type 1A, is a well-recognized target of mutations underlying a spectrum of epilepsy syndromes, and lies within an extended 12-Mb disease-associated haplotype at the familial hemiplegic migraine-3 locus, it remains to be confirmed that mutations within this gene itself cause syndromes that include migraine phenotypes. The novel T1174S missense mutation of this gene was detected segregating in a family with a heterozygous female child who presented with myoclonus and an abnormal electroencephalogram, and in her heterozygous mother, who had an ataxic migraine syndrome similar to that of her own mother. This three-generation family exhibits the broad phenotypic spectrum of the dominant neuronal hyperexcitability syndromes produced by even a given allele of this sodium channel gene. It also exhibits the second allele of this sodium channel gene associated with a migraine syndrome similar to those caused at the two other familial hemiplegic migraine loci, confirming that this gene itself, not some linked gene, is the familial hemiplegic migraine-3 locus.
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, University of California Irvine, Irvine, CA 92697-4034, USA. jjgargus@uci.edu
authors.forename: J Jay
authors.initials: JJ
authors.lastname: Gargus
authors.forename: Anne
authors.initials: A
authors.lastname: Tournay
mesh_terms: D000328:Adult; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D020325:Migraine with Aura / Q000150:complications / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009460:Neurologic Examination / Q000379:methods; D012640:Seizures / Q000150:complications / Q000235:genetics*; D012694:Serine / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics*; D013912:Threonine / Q000235:genetics
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels; D013912:Threonine; D012694:Serine