SCN1A mutations and epilepsy
Open accessAbstract
SCN1A is part of the SCN1A-SCN2A-SCN3A gene cluster on chromosome 2q24 that encodes for alpha pore forming subunits of sodium channels. The 26 exons of SCN1A are spread over 100 kb of genomic DNA. Genetic defects in the coding sequence lead to generalized epilepsy with febrile seizures plus (GEFS+) and a range of childhood epileptic encephalopathies of varied severity (e.g., SMEI). All published mutations are collated. More than 100 novel mutations are spread throughout the gene with the more debilitating usually de novo. Some clustering of mutations is observed in the C-terminus and the loops between segments 5 and 6 of the first three domains of the protein. Functional studies so far show no consistent relationship between changes to channel properties and clinical phenotype. Of all the known epilepsy genes SCN1A is currently the most clinically relevant, with the largest number of epilepsy related mutations so far characterized.
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While Dravet syndrome is differentiated by age at onset and seizure types, rare cases of EIMFS due to SCN1A mutations are described.
“While Dravet syndrome is differentiated by age at onset and seizure types, rare cases of EIMFS due to SCN1A mutations are described.26,36,38”
From <i>SCN2A</i> encephalopathy: A major cause of epilepsy of infancy with migrating focal seizures (2015) · cites this paper as [36]
Cites
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Self-citationMutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS+2
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Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations
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Na<sub>V</sub>1.1 channels and epilepsy
Catterall, W. A., Kalume, F., & Oakley, J. C. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.187484 · Cited by 428 · see citing works
<i>SCN2A</i> encephalopathy: A major cause of epilepsy of infancy with migrating focal seizures
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de Lange, I. M., Koudijs, M. J., van 't Slot, R., Gunning, B., Sonsma, A. C. M., van Gemert, L. J. J. M., Mulder, F., Carbo, E. C., van Kempen, M. J. A., Verbeek, N. E., et al. (2018) · Epilepsia · doi:10.1111/epi.14021 · Cited by 64 · see citing works
Widespread genomic influences on phenotype in Dravet syndrome, a ‘monogenic’ condition
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“3A; Table S5), with three of these being located in the C-terminus (57); all four cases are reported to have seizures, though details of seizure onset, severity, or type are not available.”
BackgroundInfluential
- Authors
- Mulley, J. C., Scheffer, I. E., Petrou, S., Dibbens, L. M., Berkovic, S. F., & Harkin, L. A.
- Affiliations
- Women's and Children's Hospital (AU)
- The University of Melbourne (AU)
- Corresponding author
- Harkin, Louise A.
- Venue
- Human Mutation
- Publisher
- Wiley
- Published
- 2005-06
- Volume
- 25
- Issue
- 6
- Pages
- 535-542
- ISSN
- 1059-7794 (ISSN-L)
- 1098-1004
- OpenAlex
- W2100497330
- Cited by
- 351
- References
- 4
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 12 · 2023: 7 · 2022: 10 · 2021: 6 · 2020: 12 · 2019: 9 · 2018: 15 · 2017: 10 · 2016: 15 · 2015: 23 · 2014: 20 · 2013: 21 · 2012: 13
- FWCI
- 3.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Human Mutation (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- SCN1A, sodium channel mutations, epilepsy, generalized epilepsy with febrile seizures plus, de novo mutations, mutation clustering, genotype-phenotype correlation, sodium channel alpha subunit
- MeSH terms
- Epilepsy, Humans, Molecular Sequence Data, Mutation, Nerve Tissue Proteins, Sodium Channels, Alternative Splicing, NAV1.1 Voltage-Gated Sodium Channel
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