Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/24023
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Type: Journal article
Title: De-novo mutations of the sodium channel gene SCN1A in alleged vaccine encephalopathy: a retrospective study
Author: Berkovic, S.
Harkin, L.
McMahon, J.
Pelekanos, J.
Zuberi, S.
Wirrell, E.
Gill, D.
Iona, X.
Mulley, J.
Scheffer, I.
Citation: The Lancet Neurology, 2006; 5(6):488-492
Publisher: Lancet Ltd
Issue Date: 2006
ISSN: 1474-4422
1474-4465
Statement of
Responsibility: 
Samuel F Berkovic, Louise Harkin, Jacinta M McMahon, James T Pelekanos, Sameer M Zuberi, Elaine C Wirrell, Deepak S Gill, Xenia Iona, John C Mulley and Ingrid E Scheffer
Abstract: BACKGROUND: Vaccination, particularly for pertussis, has been implicated as a direct cause of an encephalopathy with refractory seizures and intellectual impairment. We postulated that cases of so-called vaccine encephalopathy could have mutations in the neuronal sodium channel alpha1 subunit gene (SCN1A) because of a clinical resemblance to severe myoclonic epilepsy of infancy (SMEI) for which such mutations have been identified. METHODS: We retrospectively studied 14 patients with alleged vaccine encephalopathy in whom the first seizure occurred within 72 h of vaccination. We reviewed the relation to vaccination from source records and assessed the specific epilepsy phenotype. Mutations in SCN1A were identified by PCR amplification and denaturing high performance liquid chromatography analysis, with subsequent sequencing. Parental DNA was examined to ascertain the origin of the mutation. FINDINGS: SCN1A mutations were identified in 11 of 14 patients with alleged vaccine encephalopathy; a diagnosis of a specific epilepsy syndrome was made in all 14 cases. Five mutations predicted truncation of the protein and six were missense in conserved regions of the molecule. In all nine cases where parental DNA was available the mutations arose de novo. Clinical-molecular correlation showed mutations in eight of eight cases with phenotypes of SMEI, in three of four cases with borderline SMEI, but not in two cases with Lennox-Gastaut syndrome. INTERPRETATION: Cases of alleged vaccine encephalopathy could in fact be a genetically determined epileptic encephalopathy that arose de novo. These findings have important clinical implications for diagnosis and management of encephalopathy and, if confirmed in other cohorts, major societal implications for the general acceptance of vaccination.
Keywords: Humans; Encephalomyelitis, Acute Disseminated; Myoclonic Epilepsy, Juvenile; Seizures; Sodium Channels; Nerve Tissue Proteins; RNA, Messenger; Vaccination; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; DNA Mutational Analysis; Phenotype; Mutation; Models, Molecular; Adolescent; Child; Female; Male; NAV1.1 Voltage-Gated Sodium Channel
Description: Copyright © 2006 Elsevier Ltd All rights reserved.
RMID: 0020060648
DOI: 10.1016/S1474-4422(06)70446-X
Description (link): http://www.elsevier.com/wps/find/journaldescription.cws_home/622235/description#description
Appears in Collections:Molecular and Biomedical Science publications

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