title: Novel de novo splice-site mutation of SCN1A in a patient with partial epilepsy with febrile seizures plus.
abstract: This report describes a 4-year-old male patient experienced prolonged febrile seizures after 1 year of age, multiple febrile seizures and complex partial seizures with secondary generalization. The gene encoding voltage-gated sodium channel alpha1-subunit: SCN1A analysis revealed a heterozygous de novo one-point mutation (IVS16+2 T>C) at a splice-acceptor site. This mutation was inferred to cause truncation of the alpha1-subunit molecule and, thereby, a loss of channel function. To date, truncation mutation has been found exclusively in patients with severe myoclonic epilepsy in infancy (SMEI), although only missense mutations have been found in generalized epilepsy with febrile seizures plus (GEFS+), partial epilepsy with FS+, FS+, and FS. The patient's phenotype is consistent with that of partial epilepsy with FS+, rather than SMEI, including borderline SMEI (SMEB). We present the first case report of partial epilepsy with FS+ associated with a truncation mutation of SCN1A. The possibility exists for concomitant involvement of multiple genes other than SCN1A for seizure phenotypes.
authors.affiliation: Department of Pediatrics, Kitano Hospital, The Tazuke Kofukai Medical Institute, Ohgimachi, Kita-Ku, Osaka 530-8480, Japan. a-kumakura@kitano-hp.or.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Kumakura
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Ito
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hata
authors.forename: Norifumi
authors.initials: N
authors.lastname: Oh
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kurahashi
authors.forename: Ji-wen
authors.initials: JW
authors.lastname: Wang
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirose
mesh_terms: D001483:Base Sequence; D002675:Child, Preschool; D004569:Electroencephalography; D004831:Epilepsies, Myoclonic / Q000235:genetics; D004828:Epilepsies, Partial / Q000150:complications / Q000235:genetics*; D004829:Epilepsy, Generalized / Q000235:genetics; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D017354:Point Mutation; D022821:RNA Splice Sites; D003294:Seizures, Febrile / Q000150:complications / Q000235:genetics*; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D022821:RNA Splice Sites; C568242:SCN1A protein, human; D015222:Sodium Channels