ArticleProceedings of the National Academy of Sciences of the United States of America2001
A missense mutation of the Na+ channel alpha II subunit gene Na(v)1.2 in a patient with febrile and afebrile seizures causes channel dysfunction.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 378 citations in OpenAlex.
- Functional and pharmacological characterization of theEpilepsy & behavior reports · 2026Article
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- Excitatory Dysfunction and Phenotypic Rescue in a Human Neuronal Model ofbioRxiv : the preprint server for biology · 2026Article
- Assessing Communication Impairments in a Rare Neurodevelopmental Disorder: TheNeurology. Clinical practice · 2025Article
- Developmental mechanisms underlying pediatric epilepsy.Frontiers in neurology · 2025Review
- Two Novel Variants in theGenes · 2024Article
- GABRG2 mutations in genetic epilepsy with febrile seizures plus: structure, roles, and molecular genetics.Journal of translational medicine · 2024Review
- Expanded clinical phenotype spectrum correlates with variant function in SCN2A-related disorders.Brain : a journal of neurology · 2024Article
- Molecular Pharmacology of Selective NaACS chemical neuroscience · 2024Article
- Inversed Effects of Nav1.2 Deficiency at Medial Prefrontal Cortex and Ventral Tegmental Area for Prepulse Inhibition in Acoustic Startle Response.Molecular neurobiology · 2024Article
- Ion channels in neurodevelopment: lessons from the Integrin-KCNB1 channel complex.Neural regeneration research · 2023Article
- Therapeutic efficacy of voltage-gated sodium channel inhibitors in epilepsy.Acta epileptologica · 2023Review
- Rodent Models of Audiogenic Epilepsy: Genetic Aspects, Advantages, Current Problems and Perspectives.Biomedicines · 2022Review
- Functional correlates of clinical phenotype and severity in recurrent SCN2A variants.Communications biology · 2022Article
- Article
- NaStructure (London, England : 1993) · 2021Article
- Sodium channelopathies of skeletal muscle and brain.Physiological reviews · 2021Review
- Prickle2 and Igsf9b Coordinately Regulate the Cytoarchitecture of the Axon Initial Segment.Cell structure and function · 2020Article
- The neonatal SCN2A mutant channel mimics adult channel properties.The Journal of general physiology · 2020Article
- Pathophysiological roles and therapeutic potential of voltage-gated ion channels (VGICs) in pain associated with herpesvirus infection.Cell & bioscience · 2020Review
36 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
16 authors at 3 institutions in 3 countries.
Funding
Abstract
Generalized epilepsy with febrile seizures plus (GEFS+), a clinical subset of febrile seizures (FS), is characterized by frequent episodes beyond 6 years of age (FS+) and various types of subsequent epilepsy. Mutations in beta1 and alpha(I)-subunit genes of voltage-gated Na(+) channels have been associated with GEFS+1 and 2, respectively. Here, we report a mutation resulting in an amino acid exchange (R188W) [corrected] in the gene encoding the alpha-subunit of neuronal voltage-gated Na(+) channel type II (Na(v)1.2) in a patient with FS associated with afebrile seizures. The mutation R188W [corrected] occurring on Arg(187), a highly conserved residue among voltage-gated Na(+) channels, was not found in 224 alleles of unaffected individuals. Whole-cell patch clamp recordings on human embryonic kidney (HEK) cells expressing a rat wild-type (rNa(v)1.2) and the corresponding mutant channels showed that the mutant channel inactivated more slowly than wild-type whereas the Na(+) channel conductance was not affected. Prolonged residence in the open state of the R188W [corrected] mutant channel may augment Na(+) influx and thereby underlie the neuronal hyperexcitability that induces seizure activity. Even though a small pedigree could not show clear cosegregation with the disease phenotype, these findings strongly suggest the involvement of Na(v)1.2 in a human disease and propose the R188W [corrected] mutation as the genetic defect responsible for febrile seizures associated with afebrile seizures.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.