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Tatiana Kozhanova
Svetlana Zhilina
Tatiana Mescheryakova
Tatiana Ananieva
Evgeniya Luk`yanova
Natalia Prokop`eva
Karine Osipova
Sergrei Aivazyan
Ilia Kanivets
Fyodor Konovalov
Ekaterina Tolmacheva
Andrei Prityko
Natalia Bruhanova


Epilepsy is the most common serious neurological disorder, and there is a genetic basis in almost 50% of people with epilepsy. The diagnosis of genetic epilepsies makes to estimate reasons of seizures in the patient. Last decade has shown tremendous growth in gene sequencing technologies, which have made genetic tests available. The aim is to show significance of targeted exome sequencing and methods of data analysis in the diagnosis of hereditary syndromes leading to the development of epileptic encephalopathy. We examined 27 patients with с early EE (resistant to antiepileptic drugs), psychomotor and speech development delay in the psycho-neurological department. Targeted exome sequencing was performed for patients without a previously identified molecular diagnosis using 454 Sequencing GS Junior sequencer (Roche) and IlluminaNextSeq 500 platform. As a result of the analysis, specific epilepsy genetic variants were diagnosed in 27 patients. The greatest number of cases was due to mutations in the SCN1A gene (7/27).  The structure of mutations for other genes (mutations with a minor allele frequency of less than 0,5% are presented): ALDH7A1 (n=1), CACNA1C (n=1), CDKL5 (n=1), CNTNAP2 (n=2), DLGAP2 (n=2), DOCK7 (n=2), GRIN2B (n=2), HCN1 (n=1), NRXN1 (n=3), PCDH19 (n=1), RNASEH2B (n=2), SLC2A1 (n=1), UBE3A (n=1). The use of the exome sequencing in the genetic practice allows to significantly improve the effectiveness of medical genetic counseling, as it made possible to diagnose certain variants of genetically heterogeneous groups of diseases with similar of clinical manifestations.


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Kozhanova, T., Zhilina, S., Mescheryakova, T., Ananieva, T., Luk`yanova, E., Prokop`eva, N., Osipova, K., Aivazyan, S., Kanivets, I., Konovalov, F., Tolmacheva, E., Prityko, A., & Bruhanova, N. (2017). SIGNIFICANCE OF TARGETED EXOME SEQUENCING AND METHODS OF DATA ANALYSIS IN THE DIAGNOSIS OF GENETIC DISORDERS LEADING TO THE DEVELOPMENT OF EPILEPTIC ENCEPHALOPATHY. JOURNAL OF BIOINFORMATICS AND GENOMICS, (2 (4).
Genome analysis


Banerjee PN1, Filippi D, Allen Hauser W (2009). The descriptive epidemiology of epilepsy – a review. Epilepsy Res, 85, 31–45. doi: 10.1016/j.eplepsyres.2009.03.003

Becchetti A, Aracri P, Meneghini S, Brusco S, Amadeo A (2015). The role of nicotinic acetylcholine receptors in autosomal dominant nocturnal frontal lobe epilepsy. Front Physiol, 6, 22. doi: 10.3389/fphys.2015.00022

Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W (2010). Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia, 51, 676–685. doi: 10.1111/j.1528-1167.2010.02522.x.

Guerrini R (2006). Epilepsy in children. Lancet, 367, 499–524. DOI: 10.1016/S0140-6736(06)68182-8

Guerrini R, Marini C (2006). Genetic malformations of cortical development. Exp Brain Res, 173, 322–333. DOI: 10.1007/s00221-006-0501-z

Helbig I, Mefford HC, Sharp AJ, Guipponi M, Fichera M, Franke A (2009). 15q13.3 microdeletions increase risk of idiopathic generalized epilepsy. Nat Genet, 41, 160–162. doi: 10.1038/ng.292.

Ingo Helbiga, Ahmad N, Abou T (2016). Understanding Genotypes and Phenotypes in Epileptic Encephalopathies. Mol Syndromol, 7(4), 172-181. doi: 10.1159/000448530

Jiang T, Tan MS, Tan L, Yu JT (2014). Application of next-generation sequencing technologies in Neurology. Ann Transl Med, 2, 125. doi: 10.3978/j.issn.2305-5839.2014.11.11

Kälviäinen R, Khyuppenen J, Koskenkorva P, Eriksson K, Vanninen R, Mervaala E (2008). Clinical picture of EPM1-Unverricht-Lundborg disease. Epilepsia, 49, 549–556. doi: 10.1111/j.1528-1167.2008.01546.x

Cardoso C, Leventer RJ, Dowling JJ, Ward HL, Chung J, Petras KS (2002). Clinical and molecular basis of classical lissencephaly: Mutations in the LIS1 gene (PAFAH1B1) Hum Mutat, 19, 4–15. DOI: 10.1002/humu.10028

Lemke JR, Riesch E, Scheurenbrand T, Schubach M, Wilhelm C, Steiner I (2012). Targeted next generation sequencing as a diagnostic tool in epileptic disorders. Epilepsia, 53, 1387–1398. doi: 10.1111/j.1528-1167.2012.03516.x

Leu C, Coppola A, Sisodiya SM (2016). Progress from genome-wide association studies and copy number variant studies in epilepsy. Curr Opin Neurol, 29, 158–167. doi: 10.1097/WCO.0000000000000296

Mefford HC (2015). Clinical genetic testing in epilepsy. Epilepsy Curr, 15, 197–201. doi: 10.5698/1535-7511-15.4.197.

Michelucci R, Pasini E, Nobile C (2009). Lateral temporal lobe epilepsies: Clinical and genetic features. Epilepsia, 50(Suppl 5), 52–54. doi: 10.1111/j.1528-1167.2009.02122.x.

Mirza N, Appleton R, Burn S, Carr D, Crooks D, du Plessis D (2015). Identifying the biological pathways and erlying human focal epilepsy: From complexity to coherence to centrality. Hum Mol Genet, 24, 4306–4316. doi: 10.1093/hmg/ddv163

Moshé SL, Perucca E, Ryvlin P, Tomson T (2015). Epilepsy: New advances. Lancet, 385, 884–898. doi: 10.1016/S0140-6736(14)60456-6.

Muntoni F, Cross JH (2015). Paediatric neurology: From molecular mechanisms to targeted treatments. Lancet Neurol, 14, 16–18. doi: 10.1016/S1474-4422(14)70304-7.

Nabbout R, Prud’homme JF, Herman A, Feingold J, Brice A, Dulac O (2002). A locus for simple pure febrile seizures maps to chromosome 6q22-q24. Brain, 125(Pt 12), 2668–2680.

Ottman R, Hirose S, Jain S, Lerche H, Lopes-Cendes I, Noebels JL (2010). Genetic testing in the epilepsies – Report of the ILAE Genetics Commission. Epilepsia, 51, 655–670. doi: 10.1111/j.1528-1167.2009.02429.x.

Pal DK, Pong AW, Chung WK (2010). Genetic evaluation and counseling for epilepsy. Nat Rev Neurol, 6, 445–453. doi: 10.1038/nrneurol.2010.92

Picard F, Makrythanasis P, Navarro V, Ishida S, de Bellescize J, Ville D (2014). DEPDC5 mutations in families presenting as autosomal dominant nocturnal frontal lobe epilepsy. Neurology, 82, 2101–2106. doi: 10.1212/WNL.0000000000000488

Proposal for revised classification of epilepsies and epileptic syndromes (1989). Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia, 30, 389–99.

Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL, McGuire AL, Nussbaum RL, O'Daniel JM, Ormond KE, Rehm HL, Watson MS, Williams MS, Biesecker LG (2013). ACMG Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing. Genet Med, 15(7), 565–574. doi: 10.1038/gim.2013.73

Rehm HL, Bale SJ, Bayrak-Toydemir P, Berg JS, Brown KK, Deignan JL, Friez MJ, Funke BH, Hegde MR, Lyon E (2013). ACMG clinical laboratory standards for next-generation Sequencing. Genet Med, 15(9), 733–747. doi: 10.1038/gim.2013.92

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL (2015). Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med, 17(5), 405–424. doi: 10.1038/gim.2015.30

Staley K (2015). Molecular mechanisms of epilepsy. Nat Neurosci, 18, 367–372. doi: 10.1038/nn.3947

Thomas RH, Berkovic SF (2014). The hidden genetics of epilepsy – A clinically important new paradigm. Nat Rev Neurol, 10, 283–292. doi: 10.1038/nrneurol.2014.62

Veeramah KR, Johnstone L, Karafet TM, Wolf D, Sprissler R, Salogiannis J (2013). Exome sequencing reveals new causal mutations in children with epileptic encephalopathies. Epilepsia, 54, 1270–1281. doi: 10.1111/epi.12201

Zara F, Specchio N, Striano P, Robbiano A, Gennaro E, Paravidino R (2013). Genetic testing in benign familial epilepsies of the first year of life: Clinical and diagnostic significance. Epilepsia, 54, 425–436. doi: 10.1111/epi.12089.