Sodium channel mutations in epilepsy and other neurological disorders
Miriam H. Meisler, Jennifer A. Kearney
Miriam H. Meisler, Jennifer A. Kearney
Published August 1, 2005
Citation Information: J Clin Invest. 2005;115(8):2010-2017. https://doi.org/10.1172/JCI25466.
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Sodium channel mutations in epilepsy and other neurological disorders

Abstract

Since the first mutations of the neuronal sodium channel SCN1A were identified 5 years ago, more than 150 mutations have been described in patients with epilepsy. Many are sporadic mutations and cause loss of function, which demonstrates haploinsufficiency of SCN1A. Mutations resulting in persistent sodium current are also common. Coding variants of SCN2A, SCN8A, and SCN9A have also been identified in patients with seizures, ataxia, and sensitivity to pain, respectively. The rapid pace of discoveries suggests that sodium channel mutations are significant factors in the etiology of neurological disease and may contribute to psychiatric disorders as well.

Authors

Miriam H. Meisler, Jennifer A. Kearney

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Figure 4

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An SCN2A mutation with persistent current causes seizures in the Q54 tra...
An SCN2A mutation with persistent current causes seizures in the Q54 transgenic mouse. (A) Focal motor seizure in a Q54 mouse. (B) The GAL879–881QQQ mutation is located in the D2S4–S5 linker. (C) The mutant channel generates persistent current in Xenopus oocytes. (D) Whole-cell sodium currents recorded from CA1 hippocampal neurons from presymptomatic Q54 mice demonstrate increased persistent current. (E) Nissl-stained sections of hippocampus area CA3 reveal extensive neuronal cell loss in a Q54 mouse compared with a wild-type littermate. Adapted with permission from Neuroscience (48).