ArticleNeurobiology of disease2014
Novel SCN3A variants associated with focal epilepsy in children.
Article in Neurobiology of disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 90 citations in OpenAlex.
- Precision diagnosis ofFrontiers in genetics · 2026Article
- Voltage-Gated Sodium Channel Dysfunction in Epilepsy: Zebrafish Models for Therapeutics.Biomedicines · 2025Review
- Sevoflurane inhibition of the developmentally expressed neuronal sodium channel NaScientific reports · 2025Article
- Pathogenic variants in the polycystin pore helix cause distinct forms of channel dysfunction.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Neuronal hyperactivity in neurons derived from individuals with gray matter heterotopia.Nature communications · 2025Article
- Impaired Molecular Mechanisms Contributing to Chronic Pain in Patients with Hidradenitis Suppurativa: Exploring Potential Biomarkers and Therapeutic Targets.International journal of molecular sciences · 2025Article
- Voltage-gated sodium channels in genetic epilepsy: up and down of excitability.Journal of neurochemistry · 2024Review
- Spike-spindle coupling during sleep and its mechanism explanation in childhood focal epilepsy.Cognitive neurodynamics · 2024Article
- Unusual Voltage-Gated Sodium and Potassium Channelopathies Related to Epilepsy.Journal of clinical neurology (Seoul, Korea) · 2024Article
- Exposure to SARS-CoV-2 and Infantile Diseases.Global medical genetics · 2023Article
- Structure and Function of Sodium Channel Nav1.3 in Neurological Disorders.Cellular and molecular neurobiology · 2023Review
- Developmental and epileptic encephalopathies: from genetic heterogeneity to phenotypic continuum.Physiological reviews · 2023Review
- A nutraceutical product, extracted from Cannabis sativa, modulates voltage-gated sodium channel function.Journal of cannabis research · 2022Article
- Structural basis for modulation of human NaNature communications · 2022Article
- EAST/SeSAME Syndrome and Beyond: The Spectrum of Kir4.1- and Kir5.1-Associated Channelopathies.Frontiers in physiology · 2022Review
- Sodium channelopathies of skeletal muscle and brain.Physiological reviews · 2021Review
- Channelopathy of Dravet Syndrome and Potential Neuroprotective Effects of Cannabidiol.Journal of central nervous system disease · 2021Review
- Pathogenic in-Frame Variants inFrontiers in pharmacology · 2021Article
- Voltage Gated Sodium Channel Genes in Epilepsy: Mutations, Functional Studies, and Treatment Dimensions.Frontiers in neurology · 2021Review
- No association between SCN9A and monogenic human epilepsy disorders.PLoS genetics · 2020Observational
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Voltage-gated sodium (NaV) channels are essential for initiating and propagating action potentials in the brain. More than 800 mutations in genes encoding neuronal NaV channels including SCN1A and SCN2A have been associated with human epilepsy. Only one epilepsy-associated mutation has been identified in SCN3A encoding the NaV1.3 neuronal sodium channel. We performed a genetic screen of pediatric patients with focal epilepsy of unknown cause and identified four novel SCN3A missense variants: R357Q, D766N, E1111K and M1323V. We determined the functional consequences of these variants along with the previously reported K354Q mutation using heterologously expressed human NaV1.3. Functional defects were heterogeneous among the variants. The most severely affected was R357Q, which had a significantly smaller current density and slower activation than the wild-type (WT) channel as well as depolarized voltage dependences of activation and inactivation. Also notable was E1111K, which evoked a significantly greater level of persistent sodium current than WT channels. Interestingly, a common feature shared by all variant channels was increased current activation in response to depolarizing voltage ramps revealing a functional property consistent with conferring neuronal hyper-excitability. Discovery of a common biophysical defect among variants identified in unrelated pediatric epilepsy patients suggests that SCN3A may contribute to neuronal hyperexcitability and epilepsy.
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Registered trials
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