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An SCN2A mutation in a family with infantile seizures from Madagascar reveals an increased subthreshold Na+ current.
- Source :
-
Epilepsia (Series 4) . Sep2013, Vol. 54 Issue 9, pe117-e121. 5p. - Publication Year :
- 2013
-
Abstract
- Missense mutations in SCN2A, encoding the brain sodium channel NaV1.2, have been described in benign familial neonatal-infantile seizures ( BFNIS), a self-limiting disorder, whereas several SCN2A de novo nonsense mutations have been found in patients with more severe phenotypes including epileptic encephalopathy. We report a family with BFNIS originating from Madagascar. Onset extended from 3 to 9 months of age. Interictal EEGs were normal. In two patients, ictal electroencephalography ( EEG) studies showed partial seizure patterns with secondary generalization in one. Seizures remitted before 18 months of age, with or without medication. Intellectual development was normal. A novel missense mutation of SCN2A, c.4766A>G/p.Tyr1589Cys, was found in a highly conserved region of NaV1.2 (D4/S2-S3). Functional studies using heterologous expression in tsA201 cells and whole-cell patch clamping revealed a depolarizing shift of steady-state inactivation, increased persistent Na+ current, a slowing of fast inactivation and an acceleration of its recovery, thus a gain-of-function. Using an action potential waveform in a voltage-clamp experiment we indicated an increased inward Na+ current at subthreshold voltages, which can explain a neuronal hyperexcitability. Our results suggest that this mutation induces neuronal hyperexcitability, resulting in infantile epilepsy with favorable outcome. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00139580
- Volume :
- 54
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- Epilepsia (Series 4)
- Publication Type :
- Academic Journal
- Accession number :
- 90096270
- Full Text :
- https://doi.org/10.1111/epi.12241