Sodium channelopathies in neurodevelopmental disorders
- PMID: 33531663
- PMCID: PMC8710247
- DOI: 10.1038/s41583-020-00418-4
Sodium channelopathies in neurodevelopmental disorders
Erratum in
-
Author Correction: Sodium channelopathies in neurodevelopmental disorders.Nat Rev Neurosci. 2021 Apr;22(4):256. doi: 10.1038/s41583-021-00449-5. Nat Rev Neurosci. 2021. PMID: 33686192 No abstract available.
Abstract
The voltage-gated sodium channel α-subunit genes comprise a highly conserved gene family. Mutations of three of these genes, SCN1A, SCN2A and SCN8A, are responsible for a significant burden of neurological disease. Recent progress in identification and functional characterization of patient variants is generating new insights and novel approaches to therapy for these devastating disorders. Here we review the basic elements of sodium channel function that are used to characterize patient variants. We summarize a large body of work using global and conditional mouse mutants to characterize the in vivo roles of these channels. We provide an overview of the neurological disorders associated with mutations of the human genes and examples of the effects of patient mutations on channel function. Finally, we highlight therapeutic interventions that are emerging from new insights into mechanisms of sodium channelopathies.
Figures




Similar articles
-
Biological concepts in human sodium channel epilepsies and their relevance in clinical practice.Epilepsia. 2020 Mar;61(3):387-399. doi: 10.1111/epi.16438. Epub 2020 Feb 23. Epilepsia. 2020. PMID: 32090326
-
Comparison and optimization of in silico algorithms for predicting the pathogenicity of sodium channel variants in epilepsy.Epilepsia. 2017 Jul;58(7):1190-1198. doi: 10.1111/epi.13798. Epub 2017 May 18. Epilepsia. 2017. PMID: 28518218 Free PMC article.
-
Generation and basic characterization of a gene-trap knockout mouse model of Scn2a with a substantial reduction of voltage-gated sodium channel Nav 1.2 expression.Genes Brain Behav. 2021 Apr;20(4):e12725. doi: 10.1111/gbb.12725. Epub 2021 Jan 18. Genes Brain Behav. 2021. PMID: 33369088
-
Gene variant effects across sodium channelopathies predict function and guide precision therapy.Brain. 2022 Dec 19;145(12):4275-4286. doi: 10.1093/brain/awac006. Brain. 2022. PMID: 35037686 Free PMC article.
-
Recent advances in treatment of epilepsy-related sodium channelopathies.Eur J Paediatr Neurol. 2020 Jan;24:123-128. doi: 10.1016/j.ejpn.2019.12.009. Epub 2019 Dec 18. Eur J Paediatr Neurol. 2020. PMID: 31889633 Review.
Cited by
-
Scn1a-GFP transgenic mouse revealed Nav1.1 expression in neocortical pyramidal tract projection neurons.Elife. 2023 May 23;12:e87495. doi: 10.7554/eLife.87495. Elife. 2023. PMID: 37219072 Free PMC article.
-
Scanning mutagenesis of the voltage-gated sodium channel NaV1.2 using base editing.Cell Rep. 2023 Jun 27;42(6):112563. doi: 10.1016/j.celrep.2023.112563. Epub 2023 Jun 1. Cell Rep. 2023. PMID: 37267104 Free PMC article.
-
Immune synaptopathies: how maternal immune activation impacts synaptic function during development.EMBO J. 2023 Jul 3;42(13):e113796. doi: 10.15252/embj.2023113796. Epub 2023 May 10. EMBO J. 2023. PMID: 37161785 Free PMC article. Review.
-
Hominoid SVA-lncRNA AK057321 targets human-specific SVA retrotransposons in SCN8A and CDK5RAP2 to initiate neuronal maturation.Commun Biol. 2023 Mar 30;6(1):347. doi: 10.1038/s42003-023-04683-8. Commun Biol. 2023. PMID: 36997626 Free PMC article.
-
Interneuron FGF13 regulates seizure susceptibility via a sodium channel-independent mechanism.bioRxiv [Preprint]. 2024 Aug 19:2024.04.18.590019. doi: 10.1101/2024.04.18.590019. bioRxiv. 2024. Update in: Elife. 2025 Jan 08;13:RP98661. doi: 10.7554/eLife.98661. PMID: 38659789 Free PMC article. Updated. Preprint.
References
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources