Потенциал-зависимые натриевые каналы и их роль в этиопатогенезе эпилепсии

Эпилепсии представляют собой гетерогенную группу состояний, характеризующихся повторяющимися припадками. В настоящее время идентифицировано более 700 генов, ассоциированных с эпилепсией некоторые из них, кодируют субъединицы натриевых каналов. В связи с тенденциями развития персонализированной медицины и высокой доступности секвенирования генома, изучение вклада мутаций натриевых каналов в патогенез эпилепсии является актуальной.

ЦЕЛЬ ИССЛЕДОВАНИЯ. Анализ эпилептогенных мутаций в генах натриевых каналов по данным базы OMIM.

МЕТОДЫ: Анализ базы данных OMIM и актуальных публикаций о генетике натриевых каналов, и их связи с эпилептогенезом.

РЕЗУЛЬТАТЫ. Была дана характеристика эпилептогенных и неэпилептогенных мутаций в генах натриевых каналов с позиции системной геномики.

ЗАКЛЮЧЕНИЕ. Показана связь мутаций в генах натриевых каналов с рядом наследственных эпилепсий, включая раннюю инфантильную эпилептическую энцефалопатию. Показано, что данные исследования с использованием методов системной геномики могут иметь значение для неврологической, кардиологической и нейрохирургической практики.

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