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Missense mutations in sodium channel SCN1A and SCN2A predispose children to encephalopathy with severe febrile seizures
- Source :
- Epilepsy Research. 117:1-6
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- Objective Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a childhood encephalopathy following severe febrile seizures. The pathogenesis of AESD is considered to be fever-induced seizure susceptibility and excitotoxicity, which may be caused by sodium channel dysfunction in some cases. Here we studied whether mutations in genes encoding sodium channels, SCN1A and SCN2A , predispose children to AESD. Methods We recruited 92 AESD patients in a nationwide survey of acute encephalopathy in Japan from 2008 to 2011. We collected their genomic DNA samples, and sequenced the entire coding region of SCN1A and SCN2A . Results Five out of 92 patients (5.4%) had missense mutations either in SCN1A or SCN2A . After a preceding infection with fever, all the patients showed status epilepticus at the onset. Hemiconvulsion–hemiplegia was recognized in three patients during the acute/subacute phase. One patient had taken theophylline for the treatment of bronchial asthma just before the onset of AESD. Familial history was not remarkable except one patient with a SCN1A mutation (G1647S) whose mother had a similar episode of AESD in her childhood. A different substitution (G1674R) at the same amino acid position, as well as two other SCN1A mutations found in this study, had previously been reported in Dravet syndrome. Another SCN1A mutation (R1575C) had been detected in other types of acute encephahlitis/encephalopathy. One patient had SCN2A mutation, F328V, which had previously been reported in Dravet syndrome. Another SCN2A mutation, I172V, was novel. None of the patients were diagnosed with Dravet syndrome or genetic (generalized) epilepsy with febrile seizure plus in the following-up period. Conclusions Mutations in SCN1A and SCN2A are a predisposing factor of AESD. Altered channel activity caused by these mutations may provoke seizures and excitotoxic brain damage.
- Subjects :
- Male
medicine.medical_specialty
Encephalopathy
Mutation, Missense
Brain damage
Status epilepticus
medicine.disease_cause
Gastroenterology
Seizures, Febrile
Epilepsy
Dravet syndrome
Internal medicine
Febrile seizure
Humans
Medicine
Missense mutation
Genetic Predisposition to Disease
Child
Brain Diseases
Mutation
NAV1.2 Voltage-Gated Sodium Channel
business.industry
Infant
medicine.disease
NAV1.1 Voltage-Gated Sodium Channel
Neurology
Child, Preschool
Anesthesia
Female
Neurology (clinical)
medicine.symptom
business
Subjects
Details
- ISSN :
- 09201211
- Volume :
- 117
- Database :
- OpenAIRE
- Journal :
- Epilepsy Research
- Accession number :
- edsair.doi.dedup.....7162a62b07d730b67fcb88ae59131d5a