A prognostic model for searching genes associated with developmental and epileptic encephalopathy
A. P. Gerasimov,
I. Yu. Iourov,
V. V. Ushanov,
E. R. Barantsevich,
O. S. Kurinnaia,
K. S. Vasin,
Yu. M. Zabrodskaya,
K. A. Samochernyh,
N. E. Ivanova https://doi.org/10.56618/2071-2693_2024_16_3_18
EDN: LCYXVT
Abstract
INTRODUCTION. WHO declared epilepsy one of the most common neurological diseases. According ILAE classification developmental and epileptic encephalopathies (DEE) are generalized genetic epilepsy. DEE represent a clinically and genetically heterogeneous group of age-dependent neurologic disorders characterized by onset of refractory seizures in infancy or early childhood with delayed psychomotor development or developmental regression. Advanced genetic methods have enabled more specific delineation of these clinically defined disorders at the molecular level.
MATERIALS AND METHODS. We tried to search DEE from positions of system genomics. As the basic instrument of search resource OMIM was used (data current as of July 2024). An analysis of the success of predicting cytogenetic loci and functional groups of new genes was performed.
RESULTS. Over 2.5 years, 17 new variants of DEE were described. In 94% of cases, their genes corresponded to the functional groups we had previously published. In 53 % of cases, the genes of new forms were in the same loci as previously known genes. New data allowed us to clarify the boundaries of “hot” cytogenetic loci.
CONCLUSION. The obtained data confirm the high efficiency of the developed predictive model. Testing with new data showed 94 % compliance for physiological mechanisms and 53 % for cytogenetic loci. This model can be applied to other nosological groups.
Keywords
Supporting agencies: The study is supported by the Government Assignment No. 123021000127-7 “Development of a new technology for neurorehabilitation of patients after surgical treatment of drug-resistant epilepsy».
About the Authors
A. P. Gerasimov
V. A. Almazov National Medical Research Center
Russian Federation
Russian Federation
Alexander P. Gerasimov – Senior Researcher at the Research Laboratory of Pediatric Neurosurger
2 Akkuratova street, St. Petersburg,197341
I. Yu. Iourov
Mental Health Research Center ; Veltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery of the Pirogov Russian National Research Medical University ; Russian Medical Academy of Continuous Postgraduate Education
Russian Federation
Russian Federation
Ivan Yu. Iourov – Dr. of Sci. (Biol.), Full Professor, Professor at the Russian Academy of Sciences, Head of Laboratory named after Professor Yu. B. Yurov Molecular Genetics and Cytogenomics; Head at the Laboratory named after Professor S. G. Vorsanova Molecular Cytogenetics of Neuropsychiatric Diseases; Professor at the Department of Medical Genetics
34 Kashirskoye shosse, Moscow, 115522
3 Rakhmanovsky lane, Moscow, 127994
2/1 Barrikadnaya street, building 1, Moscow, 125993
V. V. Ushanov
V. A. Almazov National Medical Research Center
Russian Federation
Russian Federation
Vseslav V. Ushanov – Postgraduate Student at the Department of Neurosurgery
2 Akkuratova street, St. Petersburg,197341
E. R. Barantsevich
Pavlov University
Russian Federation
Russian Federation
Evgeny R. Barantsevich – Dr. of Sci. (Med.), Full Professor, Head at the Department of Neurology and Manual Medicine of Post-diploma Education
6-8 Lev Tolstoy street, St. Petersburg, 197022
O. S. Kurinnaia
Mental Health Research Center ; Veltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery of the Pirogov Russian National Research Medical University
Russian Federation
Russian Federation
Oksana S. Kurinnaia – Cand. of Sci. (Biol.), Senior Researcher at the Laboratory of Molecular Cytogenetics of Neuropsychiatric Diseases named after prof. S. G. Vorsanova; Senior Researcher at the of Laboratory of Molecular Genetics and Cytogenomics named after Professor Yu. B. Yurov
34 Kashirskoye shosse, Moscow, 115522
3 Rakhmanovsky lane, Moscow, 127994
K. S. Vasin
Mental Health Research Center ; Veltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery of the Pirogov Russian National Research Medical University
Russian Federation
Russian Federation
Vasin Kirill Sergeevich, Cand. Sci., Senior Researcher of Laboratory named after Professor YB Yurov Molecular Genetics and Cytogenomics; Researcher at the Laboratory named after Professor S. G. Vorsanova Molecular Cytogenetics of Neuropsychiatric Diseases
34 Kashirskoye shosse, Moscow, 115522
3 Rakhmanovsky lane, Moscow, 127994
Yu. M. Zabrodskaya
V. A. Almazov National Medical Research Center ; North-Western State Medical University named after I. I. Mechnikov
Russian Federation
Russian Federation
Yulia M. Zabrodskaya – Dr. of Sci. (Med.), Head at the Research Laboratory of Pathomorphology of the Nervous System; Head at the Department of Pathological anatomy
2 Akkuratova street, St. Petersburg, 197341
41 Kirochnaya street, St. Petersburg, 191015
K. A. Samochernyh
V. A. Almazov National Medical Research Center
Russian Federation
Russian Federation
Konstantin A. Samochernykh – Dr. of Sci. (Med.), Professor of the Russian Academy of Sciences, Neurosurgeon of the Highest Category at the Department of Neurosurgery for Children No. 7, Director
2 Akkuratova street, St. Petersburg, 197341
N. E. Ivanova
V. A. Almazov National Medical Research Center
Russian Federation
Russian Federation
Natalya E. Ivanova – Dr. of Sci. (Med.), Full Professor, Distinguished Doctor of the Russian Federation, Corresponding Member of the Russian Academy of Medical and Technical Sciences, Academician of the Academy of Medical and Technical Sciences, Full Member of the Petrovskaya Academy of Sciences and Arts, Member of the Board of the Association of Neurosurgeons of Russia, Member of the Board of the Babchin Association of Neurosurgeons, Member of the Geographical Society of Russia, Doctor of Functional and Ultrasound Diagnostics, Head at the Scientific Department of Russian Neurosurgical Institute, Head at the Scientific Department; Professor at the Department of Neurology and Psychiatry, Institute of Medical Education
2 Akkuratova street, St. Petersburg, 197341
References
1. World Health Organization. Epilepsy: a public health imperative. 2019. URL: https://apps.who.int/iris/handle/10665/325293 (дата обращения: 30.07.2024).
2. Scheffer I. E., Berkovic S., Capovilla G., Connolly M. B., French J., Guilhoto L., Hirsch E., Jain S., Mathern G. W., Moshé S. L., Nordli D. R., Perucca E., Tomson T., Wiebe S., Zhang Y. H., Zuberi S. M. ILAE classification of the epilepsies: Position paper of the ILAE Commission forClassification and Terminology. Epilepsia. 2017;58(4):512– 521. Doi: 10.1111/epi.13709.
3. Auvin S., Cilio M. R., Vezzani A. Current understanding and neurobiology of epileptic encephalopathies. Neurobiol Dis. 2016;92 (Pt A):72–89. Doi: 10.1016/j.nbd.2016.03.007.
4. Shbarou R., Mikati M. A. The Expanding Clinical Spectrum of Genetic Pediatric Epileptic Encephalopathies. Semin Pediatr Neurol. 2016;23(2):134–142. Doi: 10.1016/j.spen.2016.06.002.
5. Zhou P., He N., Zhang J. W., Lin Z. J., Wang J., Yan L. M., Meng H., Tang B., Li B. M., Liu X. R., Shi Y. W., Zhai Q. X., Yi Y. H., Liao W. P. Novel mutations and phenotypes of epilepsy-associated genes in epileptic encephalopathies. Genes Brain Behav. 2018;17(8):e12456. Doi: 10.1111/gbb.12456.
6. Steel D., Symonds J. D., Zuberi S. M., Brunklaus A. Dravet syndrome and its mimics: Beyond SCN1A. Epilepsia. 2017;58(11):1807–1816. Doi: 10.1111/epi.13889.
7. Foldvary-Schaefer N., Wyllie E. Epilepsy. Textbook of Clinical Neurology. 2nd ed.; eds by C. G. Goetz. Philadelphia: Saunders (pub.); 2003, pp. 1167.
8. Neurotechnologies: Collective monograph; Alekseenko S. V., Bondarko V. M., Vasiliev V. N. et al.; eds by Yu. E. Shelepin and V. N. Chikhman. SPb.: VVM; 2018. 396 p. (In Russ.). EDN: KRKMQM.
9. Galyavin S. I., Zavrazhnova A. A., Gerasimov A. P. et al. Potential-dependent sodium 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.). EDN: BXSRMA.
10. Vorsanova S. G., Demidova I. A., Kurinnaya O. S. et al. Varioma analysis of genomic pathology in children with epilepsy. Russian neurosurgical journal named after professor A. L. Polenov. 2022;14(1-2):14–16. (In Russ.).
11. Omin. URL: https://www.omim.org (дата обращения: 30.07.2024).
12. Iourov I. Y., Gerasimov A. P., Zelenova M. A. et al. Cytogenomic epileptology. Mol Cytogenet. 2023;16(1). Doi: https://doi.org/10.1186/s13039-022-00634-w.
13. Vetro A., Nielsen H. N., Holm R., Hevner R. F., Parrini E., Powis Z., Møller R. S., Bellan C., Simonati A., Lesca G., Helbig K. L., Palmer E. E., Mei D., Ballardini E., Van Haeringen A., Syrbe S., Leuzzi V., Cioni G., Curry C. J., Costain G., Santucci M., Chong K., Mancini G. M. S., Clayton-Smith J., Bigoni S., Scheffer I. E., Dobyns W. B., Vilsen B., Guerrini R. ATP1A2/A3-collaborators. ATP1A2and ATP1A3-associated early profound epileptic encephalopathy and polymicrogyria. Brain. 2021;144(5):1435–1450. Doi: 10.1093/brain/awab052.
Review
For citations:
Gerasimov A.P., Iourov I.Yu., Ushanov V.V., Barantsevich E.R., Kurinnaia O.S., Vasin K.S., Zabrodskaya Yu.M., Samochernyh K.A., Ivanova N.E. A prognostic model for searching genes associated with developmental and epileptic encephalopathy. Russian Neurosurgical Journal named after Professor A. L. Polenov. 2024;16(3):18-25. (In Russ.) https://doi.org/10.56618/2071-2693_2024_16_3_18. EDN: LCYXVT
Views:
105
Email this article 