Trends and expectations the research on the molecular background of epileptic encephalopathies – State of the art in 2017

1Panteliadis CP, Vassilyadi P, Fehlert J, Hagel C. Historical documents on epilepsy: From antiquity through the 20th century.Brain Dev. 2017;39(6):457-463. Panteliadis CP Vassilyadi P Fehlert J Hagel C Historical documents on epilepsy: From antiquity through the 20th century Brain Dev 2017396457 46310.1016/j.braindev.2017.02.00228249737Search in Google Scholar

2Sche* er IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, Hirsch E, Jain S, Mathern GW, Moshe SL, NordliDR, Perucca E, Tomson T, Wiebe S, Zhang YH, Zuberi SM. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58:512-521. Sche* er IE Berkovic S Capovilla G Connolly MB French J Guilhoto L Hirsch E Jain S Mathern GW Moshe SL Nordli DR Perucca E. Tomson T Wiebe S Zhang YH Zuberi SM. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology Epilepsia 201758512 52110.1111/epi.13709538684028276062Search in Google Scholar

3Delgado-Escueta AV, Bourgeois BF. Debate: Does genetic information in humans help us treat patients? PRO-genetic information in humans helps us treat patients. CON-genetic information does not help at all. Epilepsia 2008;49 Suppl 9:13-24. Delgado-Escueta AV Bourgeois BF. Debate: Does genetic information in humans help us treat patients? PRO-genetic information in humans helps us treat patients CON-genetic information does not help at all. Epilepsia 200849 Suppl 913 2410.1111/j.1528-1167.2008.01922.x19087113Search in Google Scholar

4Newson AJ, Leonard SJ, Hall A, Ga* CL. Known unknowns: building an ethics of uncertainty into genomic medicine. BMC Med Genomics. 2016;9:57. Newson AJ Leonard SJ Hall A Ga* CL. Known unknowns: building an ethics of uncertainty into genomic medicine BMC Med Genomics 201695710.1186/s12920-016-0219-0500956627586379Search in Google Scholar

5Andermann E. Genetic determinants in the epilepsies. [w:] Genetic of epilepsy and genetic epilepsies. 2009; 1-23, Avanzini G. And Noebels J. [red.], John Libbey Eurotext. Andermann E Genetic determinants in the epilepsies. [w:] Genetic of epilepsy and genetic epilepsies 2009 1 23 Avanzini G. And Noebels J. [red.] John Libbey EurotextSearch in Google Scholar

6Berkovic SF, Howell RA, Hay DA, Hopper JL. Epilepsies in twins: genetics of the major epilepsy syndromes. Ann Neurol. 1998;43:435-445. Berkovic SF Howell RA Hay DA Hopper JL Epilepsies in twins: genetics of the major epilepsy syndromes Ann Neurol 199843435 44510.1002/ana.4104304059546323Search in Google Scholar

7International League Against Epilepsy, Commission on Classification and Terminology. Proposal for revised Classificationof epilepsies and epileptic syndromes. Epilepsia, 1989;30:389-399. International League Against Epilepsy, Commission on Classification and Terminology Proposal for revised Classificationof epilepsies and epileptic syndromes Epilepsia 198930389 39910.1111/j.1528-1157.1989.tb05316.x2502382Search in Google Scholar

8Vadlamudi L, Andermann E, Lombroso CT, Schachter SC, Milne RL, Hopper JL, Andermann F, Berkovic SF. Epilepsy in twins: insights from unique historical data of William Lennox. Neurology 2004;62(7):1127-1133. Vadlamudi L Andermann E Lombroso CT Schachter SC Milne RL Hopper JL Andermann F Berkovic SF Epilepsy in twins: insights from unique historical data of William Lennox Neurology 20046271127 113310.1212/01.WNL.0000118201.89498.48Search in Google Scholar

9Koeleman BP. What do genetic studies tell us about the heritable basis of common epilepsy? Polygenic or complex epilepsy? Neurosci Lett. 2017;25. doi:10.1016/j. neulet.2017.03.042. Koeleman BP What do genetic studies tell us about the heritable basis of common epilepsy? Polygenic or complex epilepsy? Neurosci Lett 201725 10.1016/j.neulet.2017.03.04228347857Open DOISearch in Google Scholar

10Speed D, O’Brien TJ, Palotie A et al. Describing the genetic architecture of epilepsy through heritability analysis. Brain. 2014;137:2680-2689. Speed D O’Brien TJ Palotie A et al Describing the genetic architecture of epilepsy through heritability analysis Brain 20141372680 268910.1093/brain/awu206416303425063994Search in Google Scholar

11Sche* er IE, Berkovic SF. Generalized epilepsy with febrile seizures plus. A genetic disorder with heterogeneous clinical phenotypes. Brain. 1997;120:479-490. Sche* er IE Berkovic SF Generalized epilepsy with febrile seizures plus A genetic disorder with heterogeneous clinical phenotypes. Brain 1997120479 49010.1093/brain/120.3.4799126059Search in Google Scholar

12Claes L, Del-Favero J, Ceulemans B, Lagae L, Van Broeckhoven C, De Jonghe P. De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am J Hum Genet. 2001;68:1327-1332. Claes L Del-Favero J Ceulemans B Lagae L Van Broeckhoven C De Jonghe P. De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy Am J Hum Genet 2001681327 133210.1086/320609122611911359211Search in Google Scholar

13Johnson E. What’s new, what’s hot: the 2015 AES Hot Topic Symposium. http://www.neurologyreport.com/AES2015/johnson.php 2015 [09.2017] Johnson E What’s new, what’s hot: the 2015 AES Hot Topic Symposium http://www.neurologyreport.com/AES2015/johnson.php 2015 [09.2017]Search in Google Scholar

14Helbig I, Tayoun AA. Understanding Genotypes and Phenotypes in Epileptic Encephalopathies. Mol Syndromol. 2016;7:172-181. Helbig I Tayoun AA Understanding Genotypes and Phenotypes in Epileptic Encephalopathies Mol Syndromol 20167172 18110.1159/000448530507362227781027Search in Google Scholar

15Mefford HC, Yendle SC, Hsu C, et al. Rare copy number variants are an important cause of epileptic encephalopathies. Ann Neurol. 2011;70:974-985. Mefford HC Yendle SC Hsu C et al Rare copy number variants are an important cause of epileptic encephalopathies Ann Neurol 201170974 98510.1002/ana.22645324564622190369Search in Google Scholar

16Mefford HC Copy Number Matters in Epilepsy Epilepsy Curr 2015;15(4):180-182. Mefford HC Copy Number Matters in Epilepsy Epilepsy Curr 2015154180 18210.5698/1535-7511-15.4.180453222626316861Search in Google Scholar

17Saitsu H, Kato M, Mizuguchi T, Hamada K, Osaka H, et al. De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy. Nat Genet. 2008;40:782-788. Saitsu H Kato M Mizuguchi T Hamada K Osaka H et al De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy Nat Genet 200840782 78810.1038/ng.15018469812Search in Google Scholar

18Reutlinger C, Helbig I, Gawelczyk B, Subero JI, Tonnies H, Muhle H, Finsterwalder K, Vermeer S, Pfundt R, Sperner J, Stefanova I, Gillessen-Kaesbach G, von Spiczak S, van Baalen A, Boor R, Siebert R, Stephani U, Caliebe A. Deletions in 16p13 including GRIN2A in patients with intellectual disability, various dysmorphic features, and seizure disorders of the rolandic region. Epilepsia. 2010;51:1870-1873. Reutlinger C Helbig I Gawelczyk B Subero JI Tonnies H Muhle H Finsterwalder K Vermeer S Pfundt R Sperner J Stefanova I Gillessen-Kaesbach G von Spiczak S van Baalen A Boor R Siebert R Stephani U Caliebe A. Deletions in 16p13 including GRIN2A in patients with intellectual disability, various dysmorphic features, and seizure disorders of the rolandic region Epilepsia 2010511870 187310.1111/j.1528-1167.2010.02555.x20384727Search in Google Scholar

19Suls A, Jaehn JA, Kecskés A, Weber Y, Weckhuysen S, Craiu DC, Siekierska A, Djémié T, Afrikanova T, Gormley P, von Spiczak S, Kluger G, Iliescu CM, Talvik T, Talvik I, Meral C, Caglayan HS, Giraldez BG, Serratosa J, Lemke JR, Hofiman-Zacharska D, Szczepanik E, Barisic N, Komarek V, Hjalgrim H, Møller RS, Linnankivi T, Dimova P, Striano P, Zara F, Marini C, Guerrini R, Depienne C, Baulac S, Kuhlenbäumer G, Crawford AD, Lehesjoki AE, de Witte PA, Palotie A, Lerche H, Esguerra CV, De Jonghe P, Helbig I; EuroEPINOMICS RES Consortium.De novo loss-of-function mutations in CHD2 cause a fever-sensitive myoclonic epileptic encephalopathy sharing features with Dravet syndrome. Am J Hum Genet. 2013;93(5):967-975. Suls A Jaehn JA Kecskés A Weber Y Weckhuysen S Craiu DC Siekierska A Djémié T Afrikanova T Gormley P von Spiczak S Kluger G Iliescu CM Talvik T Talvik I Meral C Caglayan HS Giraldez BG Serratosa J Lemke JR Ho" man-Zacharska D Szczepanik E Barisic N Komarek V Hjalgrim H Møller RS Linnankivi T Dimova P Striano P Zara F Marini C Guerrini R Depienne C Baulac S Kuhlenbäumer G Crawford AD Lehesjoki AE de Witte PA Palotie A Lerche H Esguerra CV De Jonghe P Helbig I EuroEPINOMICS RES Consortium.De novo loss-of-function mutations in CHD2 cause a fever-sensitive myoclonic epileptic encephalopathy sharing features with Dravet syndrome Am J Hum Genet 2013935967 97510.1016/j.ajhg.2013.09.017382411424207121Search in Google Scholar

20Wang J, Lin ZJ, Liu L, Xu HQ, Shi YW, Yi YH, He N, Liao WP. Epilepsy-associated genes. Seizure. 2017;44:11-20. Wang J Lin ZJ Liu L Xu HQ Shi YW Yi YH He N Liao WP Epilepsy-associated genes Seizure 20174411 2010.1016/j.seizure.2016.11.03028007376Search in Google Scholar

21Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W, Engel J, French J, Glauser TA, Mathern GW, Moshé SL, Nordli D, Plouin P, Scheffer IE. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia. 2010;51(4):676-685. Berg AT Berkovic SF Brodie MJ Buchhalter J Cross JH van Emde Boas W Engel J French J Glauser TA Mathern GW Moshé SL Nordli D Plouin P Scheffer IE. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009 Epilepsia 2010514676 68510.1111/j.1528-1167.2010.02522.x20196795Search in Google Scholar

22Archer HL, Evans J, Edwards S, Colley J, Newbury-Ecob R, O’Callaghan F, Huyton M, O’Regan M, Tolmie J, Sampson J, Clarke A, Osborne J. CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients. J Med Genet. 2006;43:729-734. Archer HL Evans J Edwards S Colley J Newbury-Ecob R O’Callaghan F Huyton M O’Regan M Tolmie J Sampson J Clarke A Osborne J CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients J Med Genet 200643729 73410.1136/jmg.2006.041467256457216611748Search in Google Scholar

23Nabbout R, Chemaly N, Chipaux M, Barcia G, Bouis C, Dubouch C, Leunen D, Jambaqué I, Dulac O, Dellatolas G, Chiron C. Encephalopathy in children with Dravet syndrome is not a pure consequence of epilepsy. Orphanet J Rare Dis. 2013;8:176. Nabbout R Chemaly N Chipaux M Barcia G Bouis C Dubouch C Leunen D Jambaqué I Dulac O Dellatolas G Chiron C. Encephalopathy in children with Dravet syndrome is not a pure consequence of epilepsy Orphanet J Rare Dis 2013817610.1186/1750-1172-8-176422575724225340Search in Google Scholar

24von Deimling M, Helbig I, Marsh ED. Epileptic Encephalopathies-Clinical Syndromes and Pathophysiological Concepts. Curr Neurol Neurosci Rep. 2017;17:10. doi: 10.1007/s11910-017-0720-7. von Deimling M Helbig I Marsh ED. Epileptic Encephalopathies-Clinical Syndromes and Pathophysiological Concepts Curr Neurol Neurosci Rep 20171710 10.1007/s11910-017-0720-728229394Open DOISearch in Google Scholar

25Lynch M. Rate, molecular spectrum, and consequences of human mutation. Proc Natl Acad Sci USA. 2010;107:961-968. Lynch M Rate, molecular spectrum, and consequences of human mutation Proc Natl Acad Sci USA 2010107961 96810.1073/pnas.0912629107282431320080596Search in Google Scholar

26Vissers LE, de Ligt J, Gilissen C, Janssen I, Steehouwer M, de Vries P, van Lier B, Arts P, Wieskamp N, del Rosario M, van Bon BW, Hoischen A, de Vries BB, Brunner HG, Veltman JA. A de novo paradigm for mental retardation. Nat Genet. 2010;42(12):1109-1112. Vissers LE de Ligt J Gilissen C Janssen I Steehouwer M de Vries P van Lier B Arts P Wieskamp N del Rosario M van Bon BW Hoischen A de Vries BB Brunner HG Veltman JA. A de novo paradigm for mental retardation Nat Genet 201042121109 111210.1038/ng.71221076407Search in Google Scholar

27de Ligt J, Willemsen MH, van Bon BW, Kleefstra T, Yntema HG, Kroes T, Vulto-van Sil% out AT, Koolen DA, de Vries P, Gilissen C, del Rosario M, Hoischen A, Schefier H, de Vries BB, Brunner HG, Veltman JA, Vissers LE. Diagnostic exome sequencing in persons with severe intellectual disability. N Engl J Med. 2012;367(20):1921-1929. de Ligt J Willemsen MH van Bon BW Kleefstra T Yntema HG Kroes T Vulto-van Sil% out AT Koolen DA de Vries P Gilissen C del Rosario M Hoischen A Sche" er H de Vries BB Brunner HG Veltman JA Vissers LE. Diagnostic exome sequencing in persons with severe intellectual disability N Engl J Med 2012367201921 192910.1056/NEJMoa120652423033978Search in Google Scholar

28EuroEPINOMICS-RES Consortium; Epilepsy Phenome/Genome Project; Epi4K Consortium De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies. Am J Hum Genet. 2014;95:360-370. EuroEPINOMICS-RES Consortium; Epilepsy Phenome/Genome Project; Epi4K Consortium De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies Am J Hum Genet 201495360 37010.1016/j.ajhg.2014.08.013418511425262651Search in Google Scholar

29OMIM https://www.omim.org/ , OMIM # 308350 [09.2017] OMIM https://www.omim.org/ OMIM # 308350 [09.2017]Search in Google Scholar

30Goldberg-Stern H, Aharoni S, Afawi Z, Bennett O, Appenzeller S, Pendziwiat M, Kuhlenbäumer G, Basel-Vanagaite L, Shuper A, Korczyn AD, Helbig I. Broad phenotypic heterogeneity due to a novel SCN1A mutation in a family with genetic epilepsy with febrile seizures plus. J Child Neurol. 2014;29:221-226. Goldberg-Stern H Aharoni S Afawi Z Bennett O Appenzeller S Pendziwiat M Kuhlenbäumer G Basel-Vanagaite L Shuper A Korczyn AD Helbig I. Broad phenotypic heterogeneity due to a novel SCN1A mutation in a family with genetic epilepsy with febrile seizures plus J Child Neurol 201429221 22610.1177/088307381350901624257433Search in Google Scholar

31Steel D, Symonds JD, Zuberi SM, Brunklaus A. Dravet syndrome and its mimics: Beyond SCN1A. Epilepsia. 2017; 7. doi: 10.1111/epi.13889 Steel D Symonds JD Zuberi SM Brunklaus A Dravet syndrome and its mimics: Beyond SCN1A Epilepsia 2017 7 10.1111/epi.1388928880996Open DOISearch in Google Scholar

32Dibbens LM, Tarpey PS, Hynes K, Bayly MA, Schefier IE, Smith R, Bomar J,Sutton E, Vandeleur L, Shoubridge C, Edkins S, Turner SJ, Stevens C, O’Meara S,To+s C, Barthorpe S, Buck G, Cole J, Halliday K, Jones D, Lee R, Madison M, Mironenko T, Varian J, West S, Widaa S, Wray P, Teague J, Dicks E, Butler A, Menzies A, Jenkinson A, Shepherd R, Gusella JF, Afawi Z, Mazarib A, Neufeld MY, Kivity S, Lev D, Lerman-Sagie T, Korczyn AD, Derry CP, Sutherland GR, Friend K,Shaw M, Corbett M, Kim HG, Geschwind DH, < omas P, Haan E, Ryan S, McKee S,Berkovic SF, Futreal PA, Stratton MR, Mulley JC, Gécz J. X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment. Nature Genet. 2008;40:776-781. Dibbens LM Tarpey PS Hynes K Bayly MA Sche" er IE Smith R Bomar J,Sutton E Vandeleur L Shoubridge C Edkins S Turner SJ Stevens C O’Meara S,To+s C Barthorpe S Buck G Cole J Halliday K Jones D Lee R Madison M Mironenko T Varian J West S Widaa S Wray P Teague J Dicks E Butler A Menzies A Jenkinson A Shepherd R Gusella JF Afawi Z Mazarib A Neufeld MY Kivity S Lev D Lerman-Sagie T Korczyn AD Derry CP Sutherland GR Friend K,Shaw M Corbett M Kim HG Geschwind DH < omas P Haan E Ryan S McKee S Berkovic SF Futreal PA Stratton MR Mulley JC Gécz J X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment Nature Genet 200840776 78110.1038/ng.149275641318469813Search in Google Scholar

33Sadleir LG, Mountier EI, Gill D, Davis S, Joshi C, DeVile C,Kurian MA; DDD Study, Mandelstam S, Wirrell E, Nickels KC, MuraliHR, Carvill G, Myers CT, Mefiord HC, Schefier IE. Not all SCN1A epileptic encephalopathies are Dravet syndrome: Early profound < r226Met phenotype. Neurology. 2017 Aug 9 doi: 10.1212/WNL.0000000000004331 Sadleir LG Mountier EI Gill D Davis S Joshi C DeVile C Kurian MA DDD Study Mandelstam S Wirrell E Nickels KC Murali HR Carvill G Myers CT Mefiord HC, Schefier IE. Not all SCN1A epileptic encephalopathies are Dravet syndrome: Early profound < r226Met phenotype Neurology 2017 Aug 9 10.1212/WNL.0000000000004331558979028794249Open DOISearch in Google Scholar

34Larsen J, Carvill GL, Gardella E, Kluger G, Schmiedel G, Barisic N, Depienne C, Brilstra E, Mang Y, Nielsen JE, Kirkpatrick M, Goudie D, Goldman R, Jähn JA, Jepsen B, Gill D, Döcker M, Biskup S, McMahon JM, Koeleman B, Harris M, Braun K, de Kovel CG, Marini C, Specchio N, Djémié T, Weckhuysen S, Tommerup N, TroncosoM, Troncoso L, Bevot A, Wolff M, Hjalgrim H, Guerrini R, Schefier IE, Mefiord HC, Møller RS; EuroEPINOMICS RES Consortium CRP. < e phenotypic spectrum of SCN8A encephalopathy. Neurology 2015;84:480-489. Larsen J Carvill GL Gardella E Kluger G Schmiedel G Barisic N Depienne C Brilstra E Mang Y Nielsen JE Kirkpatrick M Goudie D Goldman R Jähn JA Jepsen B Gill D Döcker M Biskup S McMahon JM Koeleman B Harris M Braun K de Kovel CG Marini C Specchio N Djémié T Weckhuysen S Tommerup N Troncoso M Troncoso L Bevot A Wolff M Hjalgrim H Guerrini R Schefier IE, Mefiord HC, Møller RS; EuroEPINOMICS RES Consortium CRP. < e phenotypic spectrum of SCN8A encephalopathy Neurology 201584480 48910.1212/WNL.0000000000001211Search in Google Scholar

35Rakhade S, Jensen FE. Epileptogenesis in the immature brain: emerging mechanisms. Nat Rev Neurol. 2009;5:380-403. Rakhade S Jensen FE Epileptogenesis in the immature brain: emerging mechanisms Nat Rev Neurol 20095380 40310.1038/nrneurol.2009.80Search in Google Scholar

36McTague A, Howell KB, Cross JH, Kurian MA, Scheffer IE < e genetic landscape of the epileptic encephalopathies of infancy and childhood. Lancet Neurol. 2016;15;304-316. McTague A Howell KB Cross JH Kurian MA Scheffer IE < e genetic landscape of the epileptic encephalopathies of infancy and childhood Lancet Neurol 201615304 31610.1016/S1474-4422(15)00250-1Search in Google Scholar

37Olson H, Shen Y, Avallone J, Sheidley BR, Pinsky R, Bergin AM, Berry GT, Duffy FH, Eksioglu Y, Harris DJ, Hisama FM, Ho E, Irons M, Jacobsen CM, James P, Kothare S, Khwaja O, Lipton J, Loddenkemper T, Markowitz J, Maski K, Megerian JT, Neilan E, Rafialli PC, Robbins M, Roberts A, Roe E, Rollins C, Sahin M, Sarco D, Schonwald A, Smith SE, Soul J, Stoler JM, Takeoka M, Tan WH, Torres AR, Tsai P, Urion DK, Weissman L, Wolff R, Wu BL, Miller DT, Poduri A. Copy number variation plays an important role in clinical epilepsy. Ann Neurol. 2014;75:943-958. Olson H Shen Y Avallone J Sheidley BR Pinsky R Bergin AM Berry GT Duffy FH Eksioglu Y Harris DJ Hisama FM Ho E Irons M Jacobsen CM James P Kothare S Khwaja O Lipton J Loddenkemper T Markowitz J Maski K Megerian JT Neilan E Ra" alli PC Robbins M Roberts A Roe E Rollins C Sahin M Sarco D Schonwald A Smith SE Soul J Stoler JM Takeoka M Tan WH Torres AR Tsai P Urion DK Weissman L Wolff R Wu BL Miller DT Poduri A. Copy number variation plays an important role in clinical epilepsy Ann Neurol 201475943 95810.1002/ana.24178448736424811917Search in Google Scholar

38Moller RS, Dahl HA, Helbig I. < e contribution of next generation sequencing to epilepsy genetics. Expert Rev Mol Diagn. 2015;15:1531-1538. Moller RS Dahl HA Helbig I < e contribution of next generation sequencing to epilepsy genetics Expert Rev Mol Diagn 2015151531 153810.1586/14737159.2015.111313226565596Search in Google Scholar

39Mercimek-Mahmutoglu S, Patel J, Cordeiro D, Hewson S, Callen D, Donner EJ, Hahn CD, Kannu P, Kobayashi J, Minassian BA, Moharir M, Siriwardena K, Weiss SK, Weksberg R, Snead OC 3rd. Diagnostic yield of genetic testing in epileptic encephalopathy in childhood. Epilpsia 2015;56(5):707-716. Mercimek-Mahmutoglu S Patel J Cordeiro D Hewson S Callen D Donner EJ Hahn CD Kannu P Kobayashi J Minassian BA Moharir M Siriwardena K Weiss SK Weksberg R Snead OC 3rd Diagnostic yield of genetic testing in epileptic encephalopathy in childhood Epilpsia 2015565707 71610.1111/epi.1295425818041Search in Google Scholar

40Helbig KL, Farwell Hagman KD, Shinde DN, Mroske C, Powis Z, Li S, Tang S, Helbig I. Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy. Genet Med. 2016;18:898-905. Helbig KL Farwell Hagman KD Shinde DN Mroske C Powis Z Li S Tang S Helbig I. Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy Genet Med 201618898 90510.1038/gim.2015.18626795593Search in Google Scholar

41Maljevic S, Reid AR, Petrou S. Models for discovery of tergeted therapy in genetic epileptic encephalopathies. J Neurochem. 2017;10.1111/jnc.14134. Maljevic S Reid AR Petrou S Models for discovery of tergeted therapy in genetic epileptic encephalopathies J Neurochem 201710.1111/jnc.1413410.1111/jnc.1413428742937Search in Google Scholar

42Poduri A. When Should Genetic Testing Be Performed in Epilepsy Patients? Epilepsy Curr. 2017;17(1):16-22. Poduri A When Should Genetic Testing Be Performed in Epilepsy Patients? Epilepsy Curr 201717116 2210.5698/1535-7511-17.1.16534054928331464Search in Google Scholar