The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Channelopathies as a genetic cause of epilepsy
Abstract
Purpose of review This review describes the significant number of new gene associations with epilepsy syndromes that have emerged during the past year, together with additional mutations and new electrophysiological data relating to previously known gene associations. Recent findings Autosomal dominant juvenile myoclonic epilepsy was demonstrated to be a channelopathy associated with a GABAA receptor, α1 subunit mutation. Benign familial neonatal infantile seizures were delineated as another channelopathy of infancy, by molecular characterization of sodium channel, α2 subunit defects. A sodium channel, α2 subunit defect was previously found to be associated with generalized epilepsy with febrile seizures plus. Similarly, the clinical spectrum associated with potassium channel, KQT-like mutations was extended to include the channelopathy myokymia and neonatal epilepsy. Mutations in the non-ion channel genes, leucine-rich, glioma inactivated 1 gene and Aristaless related homeobox gene, have emerged as important causes of their specific syndromes, with mutations in the latter gene frequently underlying X-linked mental retardation with epilepsy. Summary All but one of the idiopathic epilepsies with a known molecular basis are channelopathies. Where the ion channel defects have been identified, however, they generally account for a minority of families and sporadic cases with the syndrome in question. The data suggest that ion channel mutations of large effect are a common cause of rare monogenic idiopathic epilepsies, but are rare causes of common epilepsies. Additive effects of genetic variation, perhaps within the same ion channel gene families, are likely to underlie the common idiopathic generalized epilepsies with complex inheritance. The genetics of epilepsy is progressing rapidly toward a more detailed molecular dissection and definition of syndromes.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Rbfox1−/− splicing changes affect transcripts encoding ion channels, neurotransmitter receptors, structural proteins and Ca2+ signalling molecules.
“However, these splicing changes affect transcripts encoding ion channels, neurotransmitter receptors, structural proteins and Ca2+ signalling molecules”
From The neurogenetics of alternative splicing (2016) · cites this paper as [133]
Many of the transcripts affected by Rbfox1−/− splicing changes are associated with seizure disorders in humans or mice.
“many of which are associated with seizure disorders in humans or mice, such as the GABAA receptor subunit Gabrg2, Grin1, the voltage-gated sodium channel Scn8a (which encodes NaV1.6), and synaptosomal-associated protein 25 (Snap25)133–137”
From The neurogenetics of alternative splicing (2016) · cites this paper as [133]
Citations
Cites
Ophoff, R. A., Terwindt, G. M., Vergouwe, M. N., van Eijk, R., Oefner, P. J., Hoffman, S. M. G., Lamerdin, J. E., Mohrenweiser, H. W., Bulman, D. E., Ferrari, M., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81373-2 · Cited by 2,337
De Novo Mutations in the Sodium-Channel Gene SCN1A Cause Severe Myoclonic Epilepsy of Infancy
Claes, L., Del-Favero, J., Ceulemans, B., Lagae, L., Van Broeckhoven, C., & De Jonghe, P. (2001) · The American Journal of Human Genetics · doi:10.1086/320609 · Cited by 1,292
A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns
Singh, N. A., Charlier, C., Stauffer, D., DuPont, B. R., Leach, R. J., Melis, R., Ronen, G. M., Bjerre, I., Quattlebaum, T., Murphy, J. V., et al. (1998) · Nature Genetics · doi:10.1038/ng0198-25 · Cited by 1,199
Steinlein, O. K., Mulley, J. C., Propping, P., Wallace, R. H., Phillips, H. A., Sutherland, G. R., Scheffer, I. E., & Berkovic, S. F. (1995) · Nature Genetics · doi:10.1038/ng1095-201 · Cited by 1,134
Self-citationA Potassium Channel Mutation in Neonatal Human Epilepsy
Biervert, C., Schroeder, B. C., Kubisch, C., Berkovic, S. F., Propping, P., Jentsch, T. J., & Steinlein, O. K. (1998) · Science · doi:10.1126/science.279.5349.403 · Cited by 1,073
Self-citationMutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS+2
Escayg, A., MacDonald, B. T., Meisler, M. H., Baulac, S., Huberfeld, G., An-Gourfinkel, I., Brice, A., LeGuern, E., Moulard, B., Chaigne, D., et al. (2000) · Nature Genetics · doi:10.1038/74159 · Cited by 996
A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family
Charlier, C., Singh, N. A., Ryan, S. G., Lewis, T. B., Reus, B. E., Leach, R. J., & Leppert, M. (1998) · Nature Genetics · doi:10.1038/ng0198-53 · Cited by 921
Absence Epilepsy in Tottering Mutant Mice Is Associated with Calcium Channel Defects
Fletcher, C., Lutz, C. M., O’Sullivan, T. N., Shaughnessy, J. D., Hawkes, R. B., Frankel, W. N., Copeland, N. G., & Jenkins, N. A. (1996) · Cell · doi:10.1016/s0092-8674(00)81381-1 · Cited by 772
Kitamura, K., Yanazawa, M., Sugiyama, N., Miura, H., Iizuka‐Kogo, A., Kusaka, M., Omichi, K., Suzuki, R., Fukui, Y., Kamiirisa, K., et al. (2002) · Nature Genetics · doi:10.1038/ng1009 · Cited by 726
Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy
Cossette, P., Liu, L., Brisebois, K., Dong, H., Lortie, A., Vanasse, M., Saint-Hilaire, J. M., Carmant, L., Verner, A., Lu, W.-Y., et al. (2002) · Nature Genetics · doi:10.1038/ng885 · Cited by 659
Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features
Kalachikov, S. M., Evgrafov, O. V., Ross, B., Winawer, M. R., Barker‐Cummings, C., Boneschi, F. M., Choi, C., Morozov, P. S., Das, K., Teplitskaya, E., et al. (2002) · Nature Genetics · doi:10.1038/ng832 · Cited by 617
Wallace, D. C., & Melov, S. (1998) · Nature Genetics · doi:10.1038/448 · Cited by 548
The nicotinic receptor β2 subunit is mutant in nocturnal frontal lobe epilepsy
Fusco, M. D., Becchetti, A., Patrignani, A., Annesi, G., Gambardella, A., Quattrone, A., Ballabio, A., Wanke, E., & Casari, G. (2000) · Nature Genetics · doi:10.1038/81566 · Cited by 447
Harkin, L. A., Bowser, D. N., Dibbens, L. M., Singh, R., Phillips, F., Wallace, R. H., Richards, M. C., Williams, D. A., Mulley, J. C., Berkovic, S. F., et al. (2002) · The American Journal of Human Genetics · doi:10.1086/338710 · Cited by 441
Self-citationMutations in the human ortholog of Aristaless cause X-linked mental retardation and epilepsy
Strømme, P., Mangelsdorf, M., Shaw, M. A., Lower, K. M., Lewis, M. E. S., Bruyèrè, H., Lütcherath, V., Gedeon, Á. K., Wallace, R. H., Scheffer, I. E., et al. (2002) · Nature Genetics · doi:10.1038/ng862 · Cited by 440
Self-citationEscayg, A., WAARD, M. M. D., Lee, D. D., Bichet, D., Wolf, P., Mayer, T., Johnston, J. L., Baloh, R. W., Sander, T., & Meisler, M. H. (2000) · The American Journal of Human Genetics · doi:10.1086/302909 · Cited by 422
Human epilepsy associated with dysfunction of the brain P/Q-type calcium channel
Jouvenceau, A., Eunson, L. H., Spauschus, A., Ramesh, V., Zuberi, S. M., Kullmann, D. M., & Hanna, M. G. (2001) · The Lancet · doi:10.1016/s0140-6736(01)05971-2 · Cited by 386
Sodium-channel defects in benign familial neonatal-infantile seizures
Heron, S. E., Crossland, K. M., Andermann, E., Phillips, H. A., Hall, A. J., Bleasel, A., Shevell, M. I., Mercho, S., Seni, M., Guiot, M., et al. (2002) · The Lancet · doi:10.1016/s0140-6736(02)09968-3 · Cited by 378
Self-citationSugawara, T., Tsurubuchi, Y., Agarwala, K. L., Ito, M., Fukuma, G., Mazaki-Miyazaki, E., Nagafuji, H., Noda, M., Imoto, K., Wada, K., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.111065098 · Cited by 378
Molecular Basis of an Inherited Epilepsy
Lossin, C., Wang, D. W., Rhodes, T. H., Vanoye, C. G., & George, A. L. (2002) · Neuron · doi:10.1016/s0896-6273(02)00714-6 · Cited by 361
Mutations in the LGI1/Epitempin gene on 10q24 cause autosomal dominant lateral temporal epilepsy
Morante‐Redolat, J. M. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.9.1119 · Cited by 345
Neuronal Sodium-Channel α1-Subunit Mutations in Generalized Epilepsy with Febrile Seizures Plus
Wallace, R. H., Scheffer, I. E., Barnett, S., Richards, M. C., Dibbens, L. M., Desai, R. R., Lerman‐Sagie, T., Lev, D., Mazarib, A., Brand, N. R., et al. (2001) · The American Journal of Human Genetics · doi:10.1086/319516 · Cited by 343
Self-citationPhillips, H. A., Favre, I., Kirkpatrick, M., Zuberi, S. M., Goudie, D. R., Heron, S. E., Scheffer, I. E., Sutherland, G. R., Berkovic, S. F., Bertrand, D., et al. (2001) · The American Journal of Human Genetics · doi:10.1086/316946 · Cited by 320
Self-citationA Splice-Site Mutation in GABRG2 Associated With Childhood Absence Epilepsy and Febrile Convulsions
Kananura, C., Haug, K., Sander, T., Runge, U., Gu, W., Hallmann, K., Rebstock, J., Heils, A., & Steinlein, O. K. (2002) · Archives of Neurology · doi:10.1001/archneur.59.7.1137 · Cited by 280
Escayg, A., Heils, A., MacDonald, B. T., Haug, K., Sander, T., & Meisler, M. H. (2001) · The American Journal of Human Genetics · doi:10.1086/319524 · Cited by 276
Myokymia and neonatal epilepsy caused by a mutation in the voltage sensor of the KCNQ2 K + channel
Dedek, K., Kunath, B., Kananura, C., Reuner, U., Jentsch, T. J., & Steinlein, O. K. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.211431298 · Cited by 252
Frequent mutations of SCN1A in severe myoclonic epilepsy in infancy
Sugawara, T., Mazaki-Miyazaki, E., Fukushima, K., 下村, 次., Fujiwara, T., Hamano, S., Inoue, Y., & Yamakawa, K. (2002) · Neurology · doi:10.1212/wnl.58.7.1122 · Cited by 235
Significant correlation of the SCN1A mutations and severe myoclonic epilepsy in infancy
Ohmori, I., Ouchida, M., Ohtsuka, Y., Oka, E., & Shimizu, K. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)00617-4 · Cited by 228
Partial and generalized epilepsy with febrile seizures plus and a novel SCN1A mutation
Abou-Khalil, B. W., Ge, Q., Desai, R. R., Ryther, R. C. C., Bazyk, A., Bailey, R., Haines, J. L., Sutcliffe, J. S., & George, A. L. (2001) · Neurology · doi:10.1212/wnl.57.12.2265 · Cited by 200
Severe Myoclonic Epilepsy of Infancy: Extended Spectrum of GEFS+?
Singh, R., Andermann, E., Whitehouse, W. P., Harvey, A. S., Keene, D. L., Seni, M., Crossland, K. M., Andermann, F., Berkovic, S. F., & Scheffer, I. E. (2001) · Epilepsia · doi:10.1046/j.1528-1157.2001.042007837.x · Cited by 199
Self-citationStrømme, P., Mangelsdorf, M., Scheffer, I. E., & Gécz, J. (2002) · Brain and Development · doi:10.1016/s0387-7604(02)00079-7 · Cited by 196
Self-citationChromosomal Abnormalities and Epilepsy: A Review for Clinicians and Gene Hunters
Singh, R., Gardner, R. J. M., Crossland, K. M., Scheffer, I. E., & Berkovic, S. F. (2002) · Epilepsia · doi:10.1046/j.1528-1157.2002.19498.x · Cited by 193
Self-citationA Novel Gene Causing a Mendelian Audiogenic Mouse Epilepsy
Skradski, S. L., Clark, A. M., Jiang, H., White, H. S., Fu, Y., & Ptáček, L. J. (2001) · Neuron · doi:10.1016/s0896-6273(01)00397-x · Cited by 189
How Mutations in the nAChRs Can Cause ADNFLE Epilepsy
Bertrand, D., Picard, F., Le Hellard, S., Weiland, S., Favre, I., Phillips, H., Bertrand, S., Berkovic, S. F., Malafosse, A., & Mulley, J. (2002) · Epilepsia · doi:10.1046/j.1528-1157.43.s.5.16.x · Cited by 173
Self-citationLGI1 is mutated in familial temporal lobe epilepsy characterized by aphasic seizures
Gu, W., Brodtkorb, E., & Steinlein, O. K. (2002) · Annals of Neurology · doi:10.1002/ana.10280 · Cited by 164
Childhood absence epilepsy and febrile seizures: a family with a GABAA receptor mutation
Marini, C., Harkin, L. A., Wallace, R. H., Mulley, J. C., Scheffer, I. E., & Berkovic, S. F. (2002) · Brain · doi:10.1093/brain/awg018 · Cited by 160
Self-citationGeneralized epilepsy with febrile seizures plus: Mutation of the sodium channel subunit SCN1B
Wallace, R. H., Scheffer, I. E., Parasivam, G., Barnett, S., Wallace, G., Sutherland, G. R., Berkovic, S. F., & Mulley, J. C. (2002) · Neurology · doi:10.1212/wnl.58.9.1426 · Cited by 153
Self-citationNa v 1.1 mutations cause febrile seizures associated with afebrile partial seizures
Sugawara, T., Mazaki-Miyazaki, E., Ito, M., Nagafuji, H., Fukuma, G., Mitsudome, A., Wada, K., Kaneko, S., Hirose, S., & Yamakawa, K. (2001) · Neurology · doi:10.1212/wnl.57.4.703 · Cited by 149
Bianchi, M. T., Song, L., Zhang, H., et al. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-13-05321.2002 · Cited by 145
A common protein interaction domain links two recently identified epilepsy genes
Scheel, H. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.15.1757 · Cited by 124
Association between the α 1a calcium channel gene CACNA1A and idiopathic generalized epilepsy
Chioza, B. A., Wilkie, H., Nashef, L. A. M., Blower, J., McCormick, D., Sham, P. C., Asherson, P. J., & MAKOFF, A. J. (2001) · Neurology · doi:10.1212/wnl.56.9.1245 · Cited by 107
Bowser, D. N., Wagner, D. A., Czajkowski, C., Cromer, B. A., Parker, M. W., Wallace, R. H., Harkin, L. A., Mulley, J. C., Marini, C., Berkovic, S. F., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.212320199 · Cited by 107
Self-citationX-linked myoclonic epilepsy with spasticity and intellectual disability
Scheffer, I. E., Wallace, R. H., Phillips, F., Hewson, P. H., Reardon, K. A., Parasivam, G., Strømme, P., Berkovic, S. F., Gécz, J., & Mulley, J. C. (2002) · Neurology · doi:10.1212/wnl.59.3.348 · Cited by 91
Self-citationFamilial pericentric inversion of chromosome 5 in a family with benign neonatal convulsions
Concolino, D., Iembo, M. A., Rossi, E., Giglio, S., Coppola, G., del Giudice, E. M., & Strisciuglio, P. (2002) · Journal of Medical Genetics · doi:10.1136/jmg.39.3.214 · Cited by 64
Cloning and mutation analysis of the human potassium channel KCNQ2 gene promoter
JianFeng, X., Fischer, C., & Steinlein, O. K. (2001) · Neuroreport · doi:10.1097/00001756-200112040-00026 · Cited by 6
Flagged first, then by citations
Research works printed but not linked: 2
- Baulac, 2001, Nat Genet, 28, 46
- Wallace, 2001, Nat Genet, 28, 49
Cited by
Sorted by citations
The neurogenetics of alternative splicing
Vuong, C. K., Black, D. L., & Zheng, S. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2016.27 · Cited by 340
The splicing regulator Rbfox1 (A2BP1) controls neuronal excitation in the mammalian brain
Gehman, L. T., Stoilov, P., Maguire, J., Damianov, A., Lin, C.-H., Shiue, L., Ares, M., Mody, I., & Black, D. L. (2011) · Nature Genetics · doi:10.1038/ng.841 · Cited by 331
SNAP‐25 in Neuropsychiatric Disorders
Corradini, I., Verderio, C., Sala, M., Wilson, M. C., & Matteoli, M. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2008.03995.x · Cited by 128
Li, M., Jancovski, N., Jafar-Nejad, P., Burbano, L. E., Rollo, B., Richards, K., Drew, L., Sedo, A., Heighway, J., Pachernegg, S., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci152079 · Cited by 115
Self-citationEpi4K: Gene discovery in 4,000 genomes
The Epi4K Consortium (2012) · Epilepsia · doi:10.1111/j.1528-1167.2012.03511.x · Cited by 85
Kapfhamer, D., Berger, K. H., Hopf, F. W., Seif, T., Kharazia, V., Bonci, A., & Heberlein, U. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1292-10.2010 · Cited by 71
Metadata
- Authors
- Mulley, J. C., Scheffer, I. E., Petrou, S., & Berkovic, S. F.
- Affiliations
- The University of Melbourne (AU)
- Corresponding author
- Mulley, John C.
- Venue
- Current Opinion in Neurology
- Published
- 2003-04
- Volume
- 16
- Issue
- 2
- Pages
- 171-176
- ISSN
- 1350-7540 (ISSN-L)
- OpenAlex
- W4240119083
- Cited by
- 214
- References
- 45
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4 · 2023: 2 · 2022: 7 · 2021: 4 · 2020: 5 · 2019: 2 · 2018: 3 · 2017: 10 · 2016: 6 · 2015: 6 · 2014: 8 · 2013: 7 · 2012: 9
- FWCI
- 14.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Neurology (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Epilepsy research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Keywords
- channelopathies, genetic epilepsy, ion channel mutations, GABA-A receptor alpha1 subunit, generalized epilepsy with febrile seizures plus, myokymia, neonatal epilepsy, LIMA1, ARX, idiopathic generalized epilepsy, genetic heterogeneity
- MeSH terms
- Chromosome Aberrations, Epilepsy, Humans, Membrane Proteins, Mutation, Nerve Tissue Proteins, Proteins, Receptors, GABA-A, Receptors, Nicotinic, Transcription Factors, Calcium Channels, Potassium Channels, Sodium Channels, Homeodomain Proteins, Calcium Channels, N-Type, Potassium Channels, Voltage-Gated, Receptors, G-Protein-Coupled, KCNQ2 Potassium Channel, Voltage-Gated Sodium Channel beta-1 Subunit, NAV1.1 Voltage-Gated Sodium Channel, NAV1.2 Voltage-Gated Sodium Channel
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
