Sodium voltage-gated channels and their role in the etiopathogenesis of epilepsy
Abstract
Epilepsies are a heterogeneous group of conditions characterized by recurrent seizures. Currently, more than 700 epilepsy-associated genes have been identified, some of them encoding sodium channel subunits. In connection with the trends in the development of personalized medicine and the high availability of genome sequencing, the study of the contribution of sodium channel mutations to the pathogenesis of epilepsy is relevant. The task of the study was analysis of epileptogenic mutations in sodium channel genes according to the OMIM database.
METHODS. Analysis of the OMIM database and current publications on the genetics of sodium channels, and their relationship with epileptogenesis.
RESULTS. Epileptogenic and non-epileptogenic mutations in sodium channel genes were characterized from the perspective of systemic genomics.
DISCUSSION. The association of mutations in sodium channel genes with a number of hereditary epilepsies, including early infantile epileptic encephalopathy (developmental and epileptic encephalopathy), has been shown. It is shown that these studies using the methods of systemic genomics can be important for neurological, cardiological and neurosurgical practice.
About the Authors
S. I. Galiavin
“Pavlov First Saint Petersburg State Medical University” Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
St. Petersburg
A. A. Zavrazhnova
“Pavlov First Saint Petersburg State Medical University” Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
St. Petersburg
A. P. Gerasimov
Almazov National Medical Research Centre Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
St. Petersburg
W. A. Khachatryan
Almazov National Medical Research Centre Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
St. Petersburg
N. E. Ivanova
Almazov National Medical Research Centre Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
St. Petersburg
References
1. Brunklaus A., du j ., Steckler F. et al. Biological concepts in human sodium channel epilepsies and their relevance in clinical practice. epilepsia. 2020 mar;61(3):387–399. https://doi.org/10.1111/epi.16438
2. guyton And Hall Textbook of mdical physiology 12th ed ISBN 978-1-4160-4574-8
3. Carlos m . Hernandez; j ohn r . r ichards p hysiology, Sodium Channels. Treasure Island (Fl ): Stat p earls p ublishing; 2021 jan-. https://www.ncbi.nlm.nih.gov/books/NBK545257/
4. Wang j, ou SW, Wang yj. distribution and function of voltage-gated sodium channels in the nervous system. Channels (Austin). 2017 Nov 02; 11(6):534–554. https://doi.org/10.1080/19336950.2017.1380758
5. oliva m , Berkovic SF, p etrou S. Sodium channels and the neurobiology of epilepsy. e pilepsia. 2012 Nov; 53(11):1849–59. https://doi.org/10.1111/j.1528–1167.2012.03631.x
6. ragsdale d S. How do mutant Nav1.1 sodium channels cause epilepsy? Brain r es r ev. 2008 j un;58(1):149–59. https://doi.org/10.1016/j.brainresrev.2008.01.003
7. onwuli d . o ., Beltran-Alvarez p. An update on transcriptional and post-translational regulation of brain voltage-gated sodium channels. Amino Acids 48, 641–651 (2016). https://doi.org/10.1007/s00726–015–2122-y
8. Baroni d ., m oran o . o n the multiple roles of the voltage gated sodium channel β1 subunit in genetic diseases. Front p harmacol. 2015 may 18;6:108. https://doi.org/10.3389/fphar.2015.00108
9. Catterall WA. Sodium Channel mutations and epilepsy. In: Noebels jl , Avoli m, rogawski mA, olsen rW, delgado- escueta Av, editors. j asper’s Basic m echanisms of the e pilepsies [Internet]. 4th ed. Bethesda (md): National Center for Biotechnology Information (uS); 2012. pmId: 22787629.
10. World Health o rganization. (2019). e pilepsy: a public health imperative. World Health o rganization. https://apps.who.int/iris/handle/10665/325293
11. Scheffer I e, Berkovic S, Capovilla g et al. I lAe classification of the epilepsies: position paper of the IlAe Commission for Classification and Terminology. e pilepsia. 2017 Apr;58(4):512–521. https://doi.org/10.1111/epi.13709
12. Falco-Walter j . j ., Scheffer I. e ., Fisher r . S. The new definition and classification of seizures and epilepsy. e pilepsy r es. 2018 jan;139:73–79. https://doi.org/10.1016/j.eplepsyres.2017.11.015
13. Catterall W. A. Forty years of Sodium Channels: Structure, Function, pharmacology, and epilepsy. Neurochem res 42, 2495–2504 (2017). https://doi.org/10.1007/s11064-017-2314-9
14. Schlachter K., g ruber-Sedlmayr u ., Stogmann e . et al. A splice site variant in the sodium channel gene SCN 1A confers risk of febrile seizures. Neurology. 2009 mar 17;72(11):974–8. https://doi.org/10.1212/01.wnl.0000344401.02915.00
15. rachael e. Stein, joshua S. Kaplan, jin li, and William A. Catterall Hippocampal deletion of Nav1.1 channels in mice causes thermal seizures and cognitive deficit characteristic of d ravet Syndrome pNAS August 13, 2019 116 (33) 16571-16576 https://doi.org/10.1073/pnas.1906833116
16. Scheffer I. e ., Nabbout r . SCN 1A-related phenotypes: e pilepsy and beyond. epilepsia. 2019 dec;60 Suppl 3: S 17-S 24. https://doi.org/10.1111/epi.16386
17. Steel d., Symonds j . d ., Zuberi S. m., Brunklaus A. d ravet syndrome and its mimics: Beyond SCN 1A. epilepsia. 2017 Nov;58(11):1807– 1816. https://doi.org/10.1111/epi.13889
18. Shbarou r, mikati mA. The expanding Clinical Spectrum of genetic p ediatric e pileptic e ncephalopathies. Semin p ediatr Neurol. 2016 may;23(2):134–42. https://doi.org/10.1016/j.spen.2016.06.002
19. vadlamudi l ., d ibbens l . m., l awrence K. m. et al. Timing of de novo mutagenesis — a twin study of sodium-channel mutations. New eng. j . med. 363: 1335–1340, 2010. https://doi.org/10.1056/Nejmoa0910752
20. ding j, li x , Tian H, Wang l, guo B, Wang y, li W, Wang F, Sun T. SCN 1A mutation-Beyond dravet Syndrome: A Systematic review and Narrative Synthesis. Front Neurol. 2021 d ec 24; 12:743726. https://doi.org/10.3389/fneur.2021.743726
21. m antegazza m , g ambardella A, r usconi r et al. Identification of an Nav1.1 sodium channel (SCN 1A) loss-of-function mutation associated with familial simple febrile seizures. proc Natl Acad Sci u SA. 2005 d ec 13;102 (50):18177–82. https://doi.org/10.1073/pnas.0506818102
22. Sadleir l.g., mountier e . I., gill d. et al. Not all SCN 1A epileptic encephalopathies are dravet syndrome: early profound Thr226 met phenotype. Neurology. 2017 Sep 5;89(10):1035–1042. https://doi.org/10.1212/WNl.0000000000004331
23. ohashi T., Akasaka N., Kobayashi y. et al. Infantile epileptic encephalopathy with a hyperkinetic movement disorder and hand stereotypies associated with a novel SCN 1A mutation. e pileptic d isord. 2014 j un;16(2):208–12. https://doi.org/10.1684/epd.2014.0649
24. ogiwara I, Ito K, Sawaishi y. et al. de novo mutations of voltage-gated sodium channel alpha II gene SCN 2A in intractable epilepsies. Neurology. 2009 Sep 29; 73(13):1046–53. https://doi.org/10.1212/WNl.0b013e3181b9cebc
25. Howell K.B., m c m ahon j . m ., Carvill g. l . et al. SCN 2A encephalopathy: A major cause of epilepsy of infancy with migrating focal seizures. Neurology. 2015 Sep 15; 85(11):958–66. https://doi.org/10.1212/WNl.0000000000001926
26. Wolff m, johannesen Km, Hedrich uBS et al. genetic and phenotypic heterogeneity suggest therapeutic implications in SCN 2A-related disorders Brain, volume 140, Issue 5, may 2017, pages 1316–1336, https://doi.org/10.1093/brain/awx054
27. liao y., Anttonen A. K., l iukkonen e . et al. SCN 2A mutation associated with neonatal epilepsy, late-onset episodic ataxia, myoclonus, and pain. Neurology. 2010 o ct 19; 75(16):1454–8. https://doi.org/10.1212/WNl.0b013e3181f8812e
28. Schwarz N., Hahn A., Bast T. et al. mutations in the sodium channel gene SCN 2A cause neonatal epilepsy with late-onset episodic ataxia. j Neurol 263, 334–343 (2016). https://doi.org/10.1007/s00415-015-7984-0
29. vanoye C. g ., g urnett C. A., Holland K. d . et al. Novel SCN 3A variants associated with focal epilepsy in children. Neurobiol d is. 2014 Feb; 62:313–22. https://doi.org/10.1016/j.nbd.2013.10.015
30. lamar T., vanoye C. g ., Calhoun j . et al. SCN 3A deficiency associated with increased seizure susceptibility. Neurobiol d is. 2017 jun;102:38–48. https://doi.org/10.1016/j.nbd.2017.02.006
31. Zaman T., Helbig I., Božović I. B. et al. mutations in SCN 3A cause early infantile epileptic encephalopathy. Ann Neurol., 2018, 83: 703–717. https://doi.org/10.1002/ana.25188
32. Wagnon j . l ., m encacci N. e ., Barker B. S. et al. p artial loss-of-function of sodium channel SCN 8A in familial isolated myoclonus. Hum m utat. 2018 j ul;39(7):965–969. https://doi.org/10.1002/humu.23547
33. Wagnon j . l ., Barker B. S., o ttolini m . et al. l oss-of-function variants of SCN 8A in intellectual disability without seizures. Neurol g enet. 2017 j un 7;3(4): e170. https://doi.org/10.1212/Nxg.0000000000000170
34. Hammer m .F., Wagnon j . l ., m efford H. C., m eisler m. H. SCN 8A- r elated e pilepsy with e ncephalopathy. 2016 Aug 25. In: Adam mp, Ardinger HH, pagon rA, Wallace Se, Bean lj H, gripp KW, m irzaa gm, Amemiya A, editors. g ener eviews ® [Internet]. Seattle (WA): university of Washington, Seattle; 1993–2022. pmId: 27559564
35. o hba C., Kato m ., Takahashi S. et al. e arly onset epileptic encephalopathy caused by de novo SCN 8A mutations. e pilepsia. 2014 jul;55(7):994–1000. https://doi.org/10.1111/epi.12668
36. de Kovel C. g ., meisler m. H., Brilstra e . H. et al. Characterization of a de novo SCN 8A mutation in a patient with epileptic encephalopathy. e pilepsy r es. 108: 1511–1518, 2014. https://doi.org/10.1016/j.eplepsyres.2014.08.020
37. Takahashi S., yamamoto S., okayama A. et al. electroclinical features of epileptic encephalopathy caused by SCN 8A mutation. pediatr Int. 2015 Aug;57(4):758–62. https://doi.org/10.1111/ped.12622
38. Blanchard m.g., Willemsen m. H., Walker j . B. et al. de novo gain-of-function and loss-of-function mutations of SCN 8A in patients with intellectual disabilities and epilepsy j ournal of m edical g enetics 2015;52:330–337. https://doi.org/10.1136/jmedgenet-2014–102813
39. Wengert e.r., Tronhjem C. e ., Wagnon j . l . et al. Biallelic inherited SCN 8A variants, a rare cause of SCN 8A-related developmental and epileptic encephalopathy. epilepsia. 2019 Nov;60(11):2277–2285. https://doi.org/10.1111/epi.16371
40. Wong j .C., Butler K. m., Shapiro l . et al. p athogenic in-Frame variants in SCN 8A: e xpanding the g enetic l andscape of SCN 8A-Associated d isease. Front p harmacol. 2021 Nov 17;12:748415. https://doi.org/10.3389/fphar.2021.748415
41. m eisler m H. SCN 8A encephalopathy: m echanisms and models. e pilepsia. 2019 d ec;60 Suppl 3(Suppl 3): S 86-S 91. https://doi.org/10.1111/epi.14703
42. gardella e., Becker F., møller r . S. et al. Benign infantile seizures and paroxysmal dyskinesia caused by an SCN 8A mutation. Ann Neurol. 2016 mar;79(3):428–36. https://doi.org/10.1002/ana.24580
43. Audenaert d ., Claes l., Ceulemans B. et al. A deletion in SCN 1B is associated with febrile seizures and early-onset absence epilepsy. Neurology. 2003 Sep 23;61(6):854–6. https://doi.org/10.1212/01.wnl.0000080362.55784.1c
44. Anand g ., Collett-White F., o rsini A. et al. Autosomal dominant SCN 8A mutation with an unusually mild phenotype. e ur j p aediatr Neurol. 2016 Sep;20(5):761–5. https://doi.org/10.1016/j.ejpn.2016.04.015
45. Wallace r.H., Scheffer I. e ., parasivam g. et al. generalized epilepsy with febrile seizures plus: mutation of the sodium channel subunit SCN 1B. Neurology. 2002 m ay 14;58(9):1426–9. https://doi.org/10.1212/wnl.58.9.1426
46. Singh r, Scheffer I e, Crossland K, Berkovic SF. generalized epilepsy with febrile seizures plus: a common childhood-onset genetic epilepsy syndrome. Ann Neurol. 1999 jan;45(1):75–81. https://doi.org/10.1002/15318249(199901)45:1<75::aid-art13>3.0.co;2-w
47. patino g .A., Claes l . r ., l opez-Santiago l .F. et al. A functional null mutation of SCN 1B in a patient with d ravet syndrome. j Neurosci. 2009 Aug 26;29(34):10764–78. https://doi.org/10.1523/jNeuroSCI.2475–09.2009
48. ramadan W., p atel N., Anazi S. et al. Confirming the recessive inheritance of SCN 1B mutations in developmental epileptic encephalopathy, Clin g enet, 2017; 92: 327–331. https://doi.org/10.1111/cge.12999
49. Kim y. o ., d ibbens l ., m arini C. et al. d o mutations in SCN 1B cause dravet syndrome? epilepsy res. 103: 97–100, 2013. https://doi.org/10.1016/j.eplepsyres.2012.10.009
50. Trump N., m cTague A, Brittain H. et al. Improving diagnosis and broadening the phenotypes in early-onset seizure and severe developmental delay disorders through gene panel analysis journal of m edical g enetics 2016;53:310–317. https://doi.org/10.1136/jmedgenet-2015–103263
Review
For citations:
Galiavin S.I., Zavrazhnova A.A., Gerasimov A.P., Khachatryan W.A., Ivanova N.E. Sodium voltage-gated channels and their role in the etiopathogenesis of epilepsy. Russian Neurosurgical Journal named after Professor A. L. Polenov. 2022;14(1-2):23-28. (In Russ.)
Views:
38
Email this article 