title: SCN1A mutation analysis in myoclonic astatic epilepsy and severe idiopathic generalized epilepsy of infancy with generalized tonic-clonic seizures.
abstract: Severe myoclonic epilepsy in infancy (SMEI), severe idiopathic generalized epilepsy of infancy (SIGEI) with generalized tonic clonic seizures (GTCS), and myoclonic astatic epilepsy (MAE) may show semiological overlaps. In GEFS+ families, all three phenotypes were found associated with mutations in the SCN1A gene. We analyzed the SCN1A gene in 20 patients with non-familial myoclonic astatic epilepsy -- including 12 probands of the original cohort used by Doose et al. in 1970 to delineate MAE. In addition, 18 patients with sporadic SIGEI -- mostly without myoclonic-astatic seizures -- were analyzed. Novel SCN1A mutations were found in 3 individuals. A frame shift resulting in an early premature stop codon in a now 35-year-old woman with a borderline phenotype of MAE and SIGEI (L433fsX449) was identified. A splice site variant (IVS18 + 5 G --> C) and a missense mutation in the conserved pore region (40736 C --> A; R946 S) were detected each in a child with SIGEI. We conclude that, independent of precise syndromic delineation, myoclonic-astatic seizures are not predictive of SCN1A mutations in sporadic myoclonic epilepsies of infancy and early childhood.
authors.affiliation: Department of Neuropediatrics, University of Giessen, Giessen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Ebach
authors.forename: H
authors.initials: H
authors.lastname: Joos
authors.forename: H
authors.initials: H
authors.lastname: Doose
authors.forename: U
authors.initials: U
authors.lastname: Stephani
authors.forename: G
authors.initials: G
authors.lastname: Kurlemann
authors.forename: B
authors.initials: B
authors.lastname: Fiedler
authors.forename: A
authors.initials: A
authors.lastname: Hahn
authors.forename: E
authors.initials: E
authors.lastname: Hauser
authors.forename: K
authors.initials: K
authors.lastname: Hundt
authors.forename: H
authors.initials: H
authors.lastname: Holthausen
authors.forename: U
authors.initials: U
authors.lastname: Müller
authors.forename: B A
authors.initials: BA
authors.lastname: Neubauer
mesh_terms: D002648:Child; D002657:Child Development; D004252:DNA Mutational Analysis; D004831:Epilepsies, Myoclonic / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D004830:Epilepsy, Tonic-Clonic / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; 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