Association of Serum Calcium Level and Sodium Channel SCN1A Mutations with Idiopathic Epilepsy among Sudanese Patients
Keywords:
SCN1A, Epilepsy, Sudan
Abstract
Background: Genetics research on humans has established that a genetic basis contributes to the susceptibility to epilepsy in a majority of cases. Al- Although many epilepsies are secondary to injury or another illness, approximately 40% are idiopathic, meaning that the original cause is unknown. It is presumed that most idiopathic epilepsies result from genetic abnormalities, with the majority likely caused by mutations in multiple currently unidentified genes. However, research has revealed a growing number of sin- gle-gene mutations that cause epilepsy.
Objective: To detect some of the genetic mutations which may cause idiopathic epilepsy.
Methods: The current study is a cross-sectional study that had been performed at Sheikh Mohamed Khair centre, Banat, Omdurman, and National Centre for Neurological Sciences (NCNS) Khartoum state, during the period 2016 to 2019. Ninety-nine participants were enrolled in this study. Demographic data were collected in a pre-designed questionnaire blood samples were analyzed for biochemical and molecular tests.
Results: Ninety-nine patients diagnosed with idiopathic epilepsy were recruited in this study. The most affected age group was 18 - 40 years accounting for 55% of patients. Females were the majority with 53%. Fifty per cent of the patients had their first seizure at the age of fewer than 5 years. Ni- ninety per cent of the patients have no Family history of epilepsy. All sequenced samples showed genetic mutations, deletion mutation was de-detected in 71% of the samples. Bioinformatics tools detected a frameshift mutation in the chain of amino acids.
Conclusion: The current study de- detected deletion mutations in the SCN1A gene (frameshift) that can cause epilepsy by changing some amino acids with residues that can affect neuronal stability indirectly.
References
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17. Asadi-Pooya, A.A., Emami, M. and Sperling, M.R. Age of Onset in Idiopath- ic (Genetic) Generalized Epilepsies: Clinical and EEG Findings in Various Age Groups. Seizure, 2012; 21, 417-421.
18. Taubøll, E., Sveberg, L. and Svalheim, S. Interactions between Hormones and Epilepsy. Seizure, 2015; 28, 3-11.
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20. Babtain, F.A. Impact of a Family History of Epilepsy on the Diagnosis of Ep- ilepsy in Southern Saudi Arabia. Seizure, 2013; 22, 542-547.
21. Oladipo, O., Lesi, F. and Ezeaka, V. Plasma Magnesium and Calcium Levels in Children with Epilepsy in Lagos. The Nigerian Postgraduate Medical Journal, 2007; 14, 26-29.
22. Bhat, M., Guru, S., Mir, R., Waza, A., Zuberi, M., Sumi, M., et al. Role of SCN1A and SCN2A Gene Polymorphisms in Epilepsy Syndromes: A Study from India. Journal of Neurology and Neuroscience, 2018; 9, Article No. 238.
23. Nabbout, R., Prud’homme, J., Herman, A., Feingold, J., Brice, A., Dulac, O., et al. () A Locus for Simple Pure Febrile Seizures Maps to Chromosome 6Q22-Q24. Brain, 2002; 125, 2668-2680. https://doi.org/10.1093/brain/awf281
24. Krauss, G. and Barañano, K. “Idiopathic” and “Genetic” Generalized Epilep- sies Intersect: “Idiopathic” and “Genetic” Generalized Epilepsies Intersect. Epilepsy currents, 2014; 14, 81-83. https://doi.org/10.5698%2F1535-7597-14.2.81
25. Kobow, K., El-Osta, A. and Blümcke, I. The Methylation Hypothesis of Phar- macoresistance in Epilepsy. Epilepsia, 2013; 54, 41-47. https://doi.org/10.1111/epi.12183
26. Mirza, N., Appleton, R., Burn, S., Carr, D., Crooks, D., du Plessis, D., et al. Identifying the Biological Pathways Underlying Human Focal Epilepsy: From Com- plexity to Coherence to Centrality. Human Molecular Genetics, 2015; 24, 4306-4316. https://doi.org/10.1093/hmg/ddv163
27. Dhiman, V. Molecular Genetics of Epilepsy: A Clinician’s Perspective. An- nals of Indian Academy of Neurology, 2017; 20, 96-102.
28. Noebels, J. Pathway-Driven Discovery of Epilepsy Genes. Nature Neuros- cience, 2015; 18, 344-350. https://doi.org/10.1038/nn.3933
29. Crabtree, G.W., Park, A.J., Gordon, J.A. and Gogos, J.A. Cytosolic Accumu- lation of L-Proline Disrupts GABA-Ergic Transmission through GAD Blockade. Cell Reports, 2016; 17, 570-582. https://doi.org/10.1016/j.celrep.2016.09.029
30. Treiman, D. GABAergic Mechanisms in Epilepsy. Epilepsia, 2001; 42, 8-12. https://doi.org/10.1046/j.1528-1157.2001.042suppl.3008.x
31. Anna, A. and Monika, G. () Splicing Mutations in Human Genetic DisorderExamples, Detection, and Confirmation. Journal of Applied Genetics, 2018; 59, 253-268. https://doi.org/10.1007/s13353-018-0444-7
32. Krnjević, K. Chemical Nature of Synaptic Transmission in Vertebrates. Phy- siological Reviews, 1974; 54, 418-540.
33. Janjua, N.A., Kabuto, H. and Mori, A. () Increased Plasma Glutamic Acid in a Genetic Model of Epilepsy. Neurochemical Research, 1992; 17, 293-296. https://doi.org/10.1007/BF00966673
34. Frezza, C. and Mauro, C. The Metabolic Challenges of Immune Cells in Health and Disease. Frontiers in Immunology, 2015; 6, Article No. 293. https://doi.org/10.3389/fimmu.2015.00293
35. Phaniendra, A., Jestadi, D.B. and Periyasamy, L. Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases. Indian Journal of Clini- cal Biochemistry, 2015; 30, 11-26. https://doi.org/10.1007/s12291-014-0446-0
36. Keshet, R. and Erez, A. Arginine and the Metabolic Regulation of Nitric oxide Synthesis in Cancer. Disease Models & Mechanisms, 2018; 11, dmm033332. https://doi.org/10.1242/dmm.033332
37. Pacher, P., Beckman, J.S. and Liaudet, L. Nitric Oxide and Peroxynitrite in Health and Disease. Physiological Reviews, 2007; 87, 315-424.
38. Shepherd, G.M. () The Synaptic Organization of the Brain. Oxford University press, Oxford 2004.
39. Farooqui, T. and Farooqui, A.A. Lipid-Mediated Oxidative Stress and In- flammation in the Pathogenesis of Parkinson’s Disease. Parkinson’s Disease, 2011, Article ID: 247467. https://doi.org/10.4061/2011/247467
40. Rigau, V., Morin, M., Rousset, M.-C., de Bock, F., Lebrun, A., Coubes, P., et al. Angiogenesis Is Associated with Blood-Brain Barrier Permeability in Temporal Lobe Epilepsy. Brain, 2007; 130, 1942-1956. https://doi.org/10.1093/brain/awm118
41. Stocker, R. and Keaney, J.F. Role of Oxidative Modifications in Atheroscle- rosis. Physiological Reviews, 2004; 84, 1381-1478.
2. LaFrance, J.W.C., Baker, G.A., Duncan, R., Goldstein, L.H. and Reuber, M. Minimum Requirements for the Diagnosis of Psychogenic Nonepileptic Seizures: A Staged Approach: A Report from the International League against Epilepsy Non- epileptic Seizures Task Force. Epilepsia, 2013; 54, 2005-2018. https://doi.org/10.1111/epi.12356
3. Irani, S.R., Bien, C.G. and Lang, B. Autoimmune Epilepsies. Current Opi- nion in Neurology, 2011; 24, 146-153. https://doi.org/10.1097/WCO.0b013e3283446f05
4. Celesia, G.G. Disorders of Membrane Channels or Channelopathies. Clinical Neurophysiology, 2001; 112, 2-18. https://doi.org/10.1016/S1388-2457(00)00496-X
5. Alexander, S.P., Fabbro, D., Kelly, E., Marrion, N., Peters, J.A., Benson, H.E., et al. The Concise Guide to PHARMACOLOGY 2015/16: Enzymes. British Jour- nal of Pharmacology, 2015; 172, 6024-6109. https://doi.org/10.1111/bph.13354
6. Marban, E., Yamagishi, T. and Tomaselli, G.F. Structure and Function of Voltage-Gated Sodium Channels. The Journal of Physiology, 1998; 508, 647-657. https://doi.org/10.1111/j.1469-7793.1998.647bp.x
7. Alekov, A.K., Rahman, M.M., Mitrovic, N., LehmannHorn, F. and Lerche, H. A Sodium Channel Mutation Causing Epilepsy in Man Exhibits Subtle Defects in Fast Inactivation and Activation In Vitro. The Journal of Physiology, 2000; 529, 533-540. https://doi.org/10.1111/j.1469-7793.2000.00533.x
8. Vilin, Y.Y. and Ruben, P.C. Slow Inactivation in Voltage-Gated Sodium Channels. Cell Biochemistry and Biophysics, 2001; 35, 171-190. https://doi.org/10.1385/CBB:35:2:171
9. Mantegazza, M. and Catterall, W.A. Voltage-Gated Na+ Channels. In: Noe- bels, J., Avoli, M., Rogawski, M., Olsen, R. and Delgado-Escueta, A., Eds., Jasper’s Basic Mechanisms of the Epilepsies, 2012; 4th Edition, Oxford University Press, Oxford, 239-389. https://doi.org/10.1093/med/9780199746545.003.0004
10. Cheah, C.S., Westenbroek, R.E., Roden, W.H., Kalume, F., Oakley, J.C., Jansen, L.A., et al. Correlations in Timing of Sodium Channel Expression, Epilepsy, and Sudden Death in Dravet Syndrome. Channels, 2013; 7, 468-472. https://doi.org/10.4161/chan.26023
11. Duflocq, A., Chareyre, F., Giovannini, M., Couraud, F. and Davenne, M. Characterization of the Axon Initial Segment (AIS) of Motor Neurons and Identifi- cation of a Para-AIS and a Juxtapara-AIS, Organized by Protein 4.1B. BMC Biology, 2011; 9, Article No. 66. https://doi.org/10.1186/1741-7007-9-66
12. Escayg, A., MacDonald, B.T., Meisler, M.H., Baulac, S., Huberfeld, G., An-Gourfinkel, I., Brice, A., LeGuern, E., Moulard, B., Chaigne, D., Buresi, C. and Malafosse, A. Mutations of SCN1A, Encoding a Neuronal Sodium Channel, in Two Fami- lies with GEFS+2. Nature Genetics, 2000; 24, 343-345.https://doi.org/10.1038/74159
13. Oliva, M., Berkovic, S.F. and Petrou, S. Sodium Channels and the Neurobi- ology of Epilepsy. Epilepsia, 2012; 53, 1849-1859. https://doi.org/10.1111/j.1528-1167.2012.03631.x
14. Fiest, K.M., Sauro, K.M., Wiebe, S., Patten, S.B., Kwon, C.-S., Dykeman, J., et al. Prevalence and Incidence of Epilepsy: A Systematic Review and Meta-Analysis of International Studies. Neurology, 2017; 88, 296-303. https://doi.org/10.1212/WNL.0000000000003509
15. Banerjee, P.N., Filippi, D. and Hauser, W.A. The Descriptive Epidemiology of Epilepsy—A Review. Epilepsy research, 2009; 85, 31-45. https://doi.org/10.1016/j.eplepsyres.2009.03.003
16. Marini, C., King, M., Archer, J.S., Newton, M.R. and Berkovic, S.F. Idiopath- ic Generalised Epilepsy of Adult Onset: Clinical Syndromes and Genetics. Journal of Neurology, Neurosurgery & Psychiatry, 2003; 74, 192-196. https://doi.org/10.1136/jnnp.74.2.192
17. Asadi-Pooya, A.A., Emami, M. and Sperling, M.R. Age of Onset in Idiopath- ic (Genetic) Generalized Epilepsies: Clinical and EEG Findings in Various Age Groups. Seizure, 2012; 21, 417-421.
18. Taubøll, E., Sveberg, L. and Svalheim, S. Interactions between Hormones and Epilepsy. Seizure, 2015; 28, 3-11.
19. Ottman, R., Barker-Cummings, C. Leibson, C., Vasoli, V., Hauser, W. and Buchhal- ter, J. Accuracy of Family History Information on Epilepsy and Other Seizure Disorders. Neurology, 2011; 76, 390-396. https://doi.org/10.1212/WNL.0b013e3182088286
20. Babtain, F.A. Impact of a Family History of Epilepsy on the Diagnosis of Ep- ilepsy in Southern Saudi Arabia. Seizure, 2013; 22, 542-547.
21. Oladipo, O., Lesi, F. and Ezeaka, V. Plasma Magnesium and Calcium Levels in Children with Epilepsy in Lagos. The Nigerian Postgraduate Medical Journal, 2007; 14, 26-29.
22. Bhat, M., Guru, S., Mir, R., Waza, A., Zuberi, M., Sumi, M., et al. Role of SCN1A and SCN2A Gene Polymorphisms in Epilepsy Syndromes: A Study from India. Journal of Neurology and Neuroscience, 2018; 9, Article No. 238.
23. Nabbout, R., Prud’homme, J., Herman, A., Feingold, J., Brice, A., Dulac, O., et al. () A Locus for Simple Pure Febrile Seizures Maps to Chromosome 6Q22-Q24. Brain, 2002; 125, 2668-2680. https://doi.org/10.1093/brain/awf281
24. Krauss, G. and Barañano, K. “Idiopathic” and “Genetic” Generalized Epilep- sies Intersect: “Idiopathic” and “Genetic” Generalized Epilepsies Intersect. Epilepsy currents, 2014; 14, 81-83. https://doi.org/10.5698%2F1535-7597-14.2.81
25. Kobow, K., El-Osta, A. and Blümcke, I. The Methylation Hypothesis of Phar- macoresistance in Epilepsy. Epilepsia, 2013; 54, 41-47. https://doi.org/10.1111/epi.12183
26. Mirza, N., Appleton, R., Burn, S., Carr, D., Crooks, D., du Plessis, D., et al. Identifying the Biological Pathways Underlying Human Focal Epilepsy: From Com- plexity to Coherence to Centrality. Human Molecular Genetics, 2015; 24, 4306-4316. https://doi.org/10.1093/hmg/ddv163
27. Dhiman, V. Molecular Genetics of Epilepsy: A Clinician’s Perspective. An- nals of Indian Academy of Neurology, 2017; 20, 96-102.
28. Noebels, J. Pathway-Driven Discovery of Epilepsy Genes. Nature Neuros- cience, 2015; 18, 344-350. https://doi.org/10.1038/nn.3933
29. Crabtree, G.W., Park, A.J., Gordon, J.A. and Gogos, J.A. Cytosolic Accumu- lation of L-Proline Disrupts GABA-Ergic Transmission through GAD Blockade. Cell Reports, 2016; 17, 570-582. https://doi.org/10.1016/j.celrep.2016.09.029
30. Treiman, D. GABAergic Mechanisms in Epilepsy. Epilepsia, 2001; 42, 8-12. https://doi.org/10.1046/j.1528-1157.2001.042suppl.3008.x
31. Anna, A. and Monika, G. () Splicing Mutations in Human Genetic DisorderExamples, Detection, and Confirmation. Journal of Applied Genetics, 2018; 59, 253-268. https://doi.org/10.1007/s13353-018-0444-7
32. Krnjević, K. Chemical Nature of Synaptic Transmission in Vertebrates. Phy- siological Reviews, 1974; 54, 418-540.
33. Janjua, N.A., Kabuto, H. and Mori, A. () Increased Plasma Glutamic Acid in a Genetic Model of Epilepsy. Neurochemical Research, 1992; 17, 293-296. https://doi.org/10.1007/BF00966673
34. Frezza, C. and Mauro, C. The Metabolic Challenges of Immune Cells in Health and Disease. Frontiers in Immunology, 2015; 6, Article No. 293. https://doi.org/10.3389/fimmu.2015.00293
35. Phaniendra, A., Jestadi, D.B. and Periyasamy, L. Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases. Indian Journal of Clini- cal Biochemistry, 2015; 30, 11-26. https://doi.org/10.1007/s12291-014-0446-0
36. Keshet, R. and Erez, A. Arginine and the Metabolic Regulation of Nitric oxide Synthesis in Cancer. Disease Models & Mechanisms, 2018; 11, dmm033332. https://doi.org/10.1242/dmm.033332
37. Pacher, P., Beckman, J.S. and Liaudet, L. Nitric Oxide and Peroxynitrite in Health and Disease. Physiological Reviews, 2007; 87, 315-424.
38. Shepherd, G.M. () The Synaptic Organization of the Brain. Oxford University press, Oxford 2004.
39. Farooqui, T. and Farooqui, A.A. Lipid-Mediated Oxidative Stress and In- flammation in the Pathogenesis of Parkinson’s Disease. Parkinson’s Disease, 2011, Article ID: 247467. https://doi.org/10.4061/2011/247467
40. Rigau, V., Morin, M., Rousset, M.-C., de Bock, F., Lebrun, A., Coubes, P., et al. Angiogenesis Is Associated with Blood-Brain Barrier Permeability in Temporal Lobe Epilepsy. Brain, 2007; 130, 1942-1956. https://doi.org/10.1093/brain/awm118
41. Stocker, R. and Keaney, J.F. Role of Oxidative Modifications in Atheroscle- rosis. Physiological Reviews, 2004; 84, 1381-1478.
Published
2022-12-23
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