title: Patients with a sodium channel alpha 1 gene mutation show wide phenotypic variation.
abstract: We investigated the roles of mutations in voltage-gated sodium channel alpha 1 subunit gene (SCN1A) in epilepsies and psychiatric disorders. The SCN1A gene was screened for mutations in three unrelated Japanese families with generalized epilepsy with febrile seizure plus (GEFS+), febrile seizure with myoclonic seizures, or intractable childhood epilepsy with generalized tonic-clonic seizures (ICEGTC). In the family with GEFS+, one individual was affected with panic disorder and seizures, and another individual was diagnosed with Asperger syndrome and seizures. The novel mutation V1366I was found in all probands and patients with psychiatric disorders of the three families. These results suggest that SCN1A mutations may confer susceptibility to psychiatric disorders in addition to variable epileptic seizures. Unidentified modifiers may play critical roles in determining the ultimate phenotype of patients with sodium channel mutations.
authors.affiliation: Division of Neurology, Kanagawa Children's Medical Center, Yokohama 232-8555, Japan. kcmc_ho@cameo.plala.or.jp
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Osaka
authors.forename: Ikuo
authors.initials: I
authors.lastname: Ogiwara
authors.forename: Emi
authors.initials: E
authors.lastname: Mazaki
authors.forename: Nami
authors.initials: N
authors.lastname: Okamura
authors.forename: Sumimasa
authors.initials: S
authors.lastname: Yamashita
authors.forename: Mizue
authors.initials: M
authors.lastname: Iai
authors.forename: Michiko
authors.initials: M
authors.lastname: Yamada
authors.forename: Kenji
authors.initials: K
authors.lastname: Kurosawa
authors.forename: Hiroko
authors.initials: H
authors.lastname: Iwamoto
authors.forename: Norio
authors.initials: N
authors.lastname: Yasui-Furukori
authors.forename: Sunao
authors.initials: S
authors.lastname: Kaneko
authors.forename: Tateki
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Yushi
authors.initials: Y
authors.lastname: Inoue
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamakawa
mesh_terms: D000328:Adult; D002648:Child; D004252:DNA Mutational Analysis; D004827:Epilepsy / Q000145:classification / Q000150:complications / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007532:Isoleucine / Q000235:genetics; D008297:Male; D009154:Mutation; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D015222:Sodium Channels / Q000235:genetics*; D014633:Valine / Q000235:genetics
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels; D007532:Isoleucine; D014633:Valine