title: Temporal lobe epilepsy and GEFS+ phenotypes associated with SCN1B mutations.
abstract: SCN1B, the gene encoding the sodium channel beta 1 subunit, was the first gene identified for generalized epilepsy with febrile seizures plus (GEFS+). Only three families have been published with SCN1B mutations. Here, we present four new families with SCN1B mutations and characterize the associated phenotypes. Analysis of SCN1B was performed on 402 individuals with various epilepsy syndromes. Four probands with missense mutations were identified. Detailed electroclinical phenotyping was performed on all available affected family members including quantitative MR imaging in those with temporal lobe epilepsy (TLE). Two new families with the original C121W SCN1B mutation were identified; novel mutations R85C and R85H were each found in one family. The following phenotypes occurred in the six families with SCN1B missense mutations: 22 febrile seizures, 20 febrile seizures plus, five TLE, three other GEFS+ phenotypes, two unclassified and ten unaffected individuals. All individuals with confirmed TLE had the C121W mutation; two underwent temporal lobectomy (one with hippocampal sclerosis and one without) and both are seizure free. We confirm the role of SCN1B in GEFS+ and show that the GEFS+ spectrum may include TLE alone. TLE with an SCN1B mutation is not a contraindication to epilepsy surgery.
authors.affiliation: Department of Medicine (Neurology), University of Melbourne, Melbourne, Victoria, Australia. scheffer@unimelb.edu.au
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
authors.forename: Louise A
authors.initials: LA
authors.lastname: Harkin
authors.forename: Bronwyn E
authors.initials: BE
authors.lastname: Grinton
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Dibbens
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Turner
authors.forename: Marta A
authors.initials: MA
authors.lastname: Zielinski
authors.forename: Ruwei
authors.initials: R
authors.lastname: Xu
authors.forename: Graeme
authors.initials: G
authors.lastname: Jackson
authors.forename: Judith
authors.initials: J
authors.lastname: Adams
authors.forename: Mary
authors.initials: M
authors.lastname: Connellan
authors.forename: Steven
authors.initials: S
authors.lastname: Petrou
authors.forename: R Mark
authors.initials: RM
authors.lastname: Wellard
authors.forename: Regula S
authors.initials: RS
authors.lastname: Briellmann
authors.forename: Robyn H
authors.initials: RH
authors.lastname: Wallace
authors.forename: John C
authors.initials: JC
authors.lastname: Mulley
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Berkovic
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D004829:Epilepsy, Generalized / Q000235:genetics*; D004833:Epilepsy, Temporal Lobe / Q000235:genetics*; D005192:Family Health; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics; D012640:Seizures / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics*; D062547:Voltage-Gated Sodium Channel beta-1 Subunit
chemical_list: C470379:SCN1B protein, human; D015222:Sodium Channels; D062547:Voltage-Gated Sodium Channel beta-1 Subunit