No association between SCN9A and monogenic human epilepsy disorders
Autoři:
James Fasham aff001; Joseph S. Leslie aff001; Jamie W. Harrison aff001; James Deline aff004; Katie B. Williams aff005; Ashley Kuhl aff005; Jessica Scott Schwoerer aff005; Harold E. Cross aff006; Andrew H. Crosby aff001; Emma L. Baple aff001
Působiště autorů:
RILD Wellcome Wolfson Centre, University of Exeter Medical School, Royal Devon & Exeter NHS Foundation Trust, Barrack Road, Exeter, United Kingdom
aff001; Peninsula Clinical Genetics Service, Royal Devon & Exeter Hospital, Gladstone Road, Exeter, United Kingdom
aff002; University of Exeter, Department of Biosciences, Exeter, United Kingdom
aff003; Center for Special Children, La Farge Medical Clinic-VMH, La Farge, Wisconsin, United States of America
aff004; Department of Pediatrics, University of Wisconsin, Madison, Wisconsin, United States of America
aff005; Department of Ophthalmology, University of Arizona College of Medicine, Tucson, Arizona, United States of America
aff006
Vyšlo v časopise:
No association between SCN9A and monogenic human epilepsy disorders. PLoS Genet 16(11): e1009161. doi:10.1371/journal.pgen.1009161
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1009161
Souhrn
Many studies have demonstrated the clinical utility and importance of epilepsy gene panel testing to confirm the specific aetiology of disease, enable appropriate therapeutic interventions, and inform accurate family counselling. Previously, SCN9A gene variants, in particular a c.1921A>T p.(Asn641Tyr) substitution, have been identified as a likely autosomal dominant cause of febrile seizures/febrile seizures plus and other monogenic seizure phenotypes indistinguishable from those associated with SCN1A, leading to inclusion of SCN9A on epilepsy gene testing panels. Here we present serendipitous findings of genetic studies that identify the SCN9A c.1921A>T p.(Asn641Tyr) variant at high frequency in the Amish community in the absence of such seizure phenotypes. Together with findings in UK Biobank these data refute an association of SCN9A with epilepsy, which has important clinical diagnostic implications.
Klíčová slova:
Alleles – Clinical genetics – Epilepsy – Genetics – Genomics – Heterozygosity – Human genetics – Protein domains
Zdroje
1. Kearney H, Byrne S, Cavalleri GL, Delanty N. Tackling Epilepsy With High-definition Precision Medicine: A Review. JAMA Neurol. 2019;76(9):1109–1116 doi: 10.1001/jamaneurol.2019.2384 31380988
2. Strande NT, Riggs ER, Buchanan AH, Ceyhan-Birsoy O, DiStefano M, Dwight SS, et al. Evaluating the Clinical Validity of Gene-Disease Associations: An Evidence-Based Framework Developed by the Clinical Genome Resource. Am J Hum Genet. 2017;100(6):895–906 doi: 10.1016/j.ajhg.2017.04.015 28552198
3. Martin AR, Williams E, Foulger RE, Leigh S, Daugherty LC, Niblock O, et al. PanelApp crowdsources expert knowledge to establish consensus diagnostic gene panels. Nature genetics. 2019;51(11):1560–5 doi: 10.1038/s41588-019-0528-2 31676867
4. Balestrini S, Sisodiya SM. Pharmacogenomics in epilepsy. Neurosci Lett. 2018;667:27–39 doi: 10.1016/j.neulet.2017.01.014 28082152
5. Wilmshurst JM, Gaillard WD, Vinayan KP, Tsuchida TN, Plouin P, Van Bogaert P, et al. Summary of recommendations for the management of infantile seizures: Task Force Report for the ILAE Commission of Pediatrics. Epilepsia. 2015;56(8):1185–97 doi: 10.1111/epi.13057 26122601
6. Wheless JW, Fulton SP, Mudigoudar BD. Dravet Syndrome: A Review of Current Management. Pediatric neurology. 2020;107:28–40 doi: 10.1016/j.pediatrneurol.2020.01.005 32165031
7. Singh NA, Pappas C, Dahle EJ, Claes LR, Pruess TH, De Jonghe P, et al. A role of SCN9A in human epilepsies, as a cause of febrile seizures and as a potential modifier of Dravet syndrome. PLoS genetics. 2009;5(9):e1000649 doi: 10.1371/journal.pgen.1000649 19763161
8. Mantegazza M, Gambardella A, Rusconi R, Schiavon E, Annesi F, Cassulini RR, et al. Identification of an Nav1.1 sodium channel (SCN1A) loss-of-function mutation associated with familial simple febrile seizures. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(50):18177–82 doi: 10.1073/pnas.0506818102 16326807
9. Bonanni P, Malcarne M, Moro F, Veggiotti P, Buti D, Ferrari AR, et al. Generalized epilepsy with febrile seizures plus (GEFS+): clinical spectrum in seven Italian families unrelated to SCN1A, SCN1B, and GABRG2 gene mutations. Epilepsia. 2004;45(2):149–58 doi: 10.1111/j.0013-9580.2004.04303.x 14738422
10. Møller RS, Schneider LM, Hansen CP, Bugge M, Ullmann R, Tommerup N, et al. Balanced translocation in a patient with severe myoclonic epilepsy of infancy disrupts the sodium channel gene SCN1A. Epilepsia. 2008;49(6):1091–4 doi: 10.1111/j.1528-1167.2008.01550.x 18294202
11. Oakley JC, Kalume F, Yu FH, Scheuer T, Catterall WA. Temperature- and age-dependent seizures in a mouse model of severe myoclonic epilepsy in infancy. Proceedings of the National Academy of Sciences. 2009;106(10):3994–9
12. Yang C, Hua Y, Zhang W, Xu J, Xu L, Gao F, et al. Variable epilepsy phenotypes associated with heterozygous mutation in the SCN9A gene: report of two cases. Neurological Sciences. 2018;39(6):1113–5 doi: 10.1007/s10072-018-3300-y 29500686
13. Banfi P, Coll M, Oliva A, Alcalde M, Striano P, Mauri M, et al. Lamotrigine induced Brugada-pattern in a patient with genetic epilepsy associated with a novel variant in SCN9A. Gene. 2020;754:144847 doi: 10.1016/j.gene.2020.144847 32531456
14. Cen Z, Lou Y, Guo Y, Wang J, Feng J. Q10R mutation in SCN9A gene is associated with generalized epilepsy with febrile seizures plus. Seizure. 2017;50:186–8 doi: 10.1016/j.seizure.2017.06.023 28704742
15. Liu Z, Ye X, Qiao P, Luo W, Wu Y, He Y, et al. G327E mutation in SCN9A gene causes idiopathic focal epilepsy with Rolandic spikes: a case report of twin sisters. Neurological Sciences. 2019;40(7):1457–60 doi: 10.1007/s10072-019-03752-3 30834459
16. Zhang T, Chen M, Zhu A, Zhang X, Fang T. Novel mutation of SCN9A gene causing generalized epilepsy with febrile seizures plus in a Chinese family. Neurol Sci. 2020; 41(7): 1913–1917.
17. Alves RM, Uva P, Veiga MF, Oppo M, Zschaber FCR, Porcu G, et al. Novel ANKRD11 gene mutation in an individual with a mild phenotype of KBG syndrome associated to a GEFS+ phenotypic spectrum: a case report. BMC Med Genet. 2019;20(1):16 doi: 10.1186/s12881-019-0745-7 30642272
18. Mulley JC, Hodgson B, McMahon JM, Iona X, Bellows S, Mullen SA, et al. Role of the sodium channel SCN9A in genetic epilepsy with febrile seizures plus and Dravet syndrome. Epilepsia. 2013;54(9):e122–e6 doi: 10.1111/epi.12323 23895530
19. Iffland PH 2nd, Carson V, Bordey A, Crino PB. GATORopathies: The role of amino acid regulatory gene mutations in epilepsy and cortical malformations. Epilepsia. 2019;60(11):2163–73 doi: 10.1111/epi.16370 31625153
20. Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alföldi J, Wang Q, et al. Variation across 141,456 human exomes and genomes reveals the spectrum of loss-of-function intolerance across human protein-coding genes. bioRxiv. 2019:531210
21. Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature. 2016;536(7616):285–91 doi: 10.1038/nature19057 27535533
22. Jung KS, Hong K-W, Jo HY, Choi J, Ban H-J, Cho SB, et al. KRGDB: the large-scale variant database of 1722 Koreans based on whole genome sequencing. Database. 2020;2020
23. Abouelhoda M, Faquih T, El-Kalioby M, Alkuraya FS. Revisiting the morbid genome of Mendelian disorders. Genome biology. 2016;17(1):235 doi: 10.1186/s13059-016-1102-1 27884173
24. Kaplanis J., Samocha K.E., Wiel L. et al. Evidence for 28 genetic disorders discovered by combining healthcare and research data. Nature (2020). doi: 10.1038/s41586-020-2832-5 33057194
25. Buniello A, MacArthur JAL, Cerezo M, Harris LW, Hayhurst J, Malangone C, et al. The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019. Nucleic acids research. 2019;47(D1):D1005–D12 doi: 10.1093/nar/gky1120 30445434
26. Mulley JC, Scheffer IE, Petrou S, Dibbens LM, Berkovic SF, Harkin LA. SCN1A mutations and epilepsy. Human mutation. 2005;25(6):535–42 doi: 10.1002/humu.20178 15880351
27. Berkovic SF, Heron SE, Giordano L, Marini C, Guerrini R, Kaplan RE, et al. Benign familial neonatal-infantile seizures: characterization of a new sodium channelopathy. Annals of neurology. 2004;55(4):550–7 doi: 10.1002/ana.20029 15048894
28. Vanoye CG, Gurnett CA, Holland KD, George AL Jr., Kearney JA. Novel SCN3A variants associated with focal epilepsy in children. Neurobiol Dis. 2014;62:313–22 doi: 10.1016/j.nbd.2013.10.015 24157691
29. Faber CG, Hoeijmakers JGJ, Ahn H-S, Cheng X, Han C, Choi J-S, et al. Gain of function Naν1.7 mutations in idiopathic small fiber neuropathy. Annals of neurology. 2012;71(1):26–39 doi: 10.1002/ana.22485 21698661
30. Yang Y, Wang Y, Li S, Xu Z, Li H, Ma L, et al. Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia. Journal of medical genetics. 2004;41(3):171–4 doi: 10.1136/jmg.2003.012153 14985375
31. Michiels JJ, te Morsche RHM, Jansen JBMJ, Drenth JPH. Autosomal Dominant Erythermalgia Associated With a Novel Mutation in the Voltage-Gated Sodium Channel α Subunit Nav1.7. Archives of neurology. 2005;62(10):1587–90 doi: 10.1001/archneur.62.10.1587 16216943
32. Cox JJ, Reimann F, Nicholas AK, Thornton G, Roberts E, Springell K, et al. An SCN9A channelopathy causes congenital inability to experience pain. Nature. 2006;444(7121):894–8 doi: 10.1038/nature05413 17167479
33. ClinGen. SCN9A - epilepsy 2018 [cited 2020 11/08/2020]. Available from: https://search.clinicalgenome.org/kb/genes/HGNC:10597.
34. Athena Diagnostics. Epilepsy Advanced Sequencing and CNV Evaluation 2020 [21/10/2020]. Available from: https://www.athenadiagnostics.com/view-full-catalog/e/epilepsy-advanced-sequencing-and-cnv-evaluation.
35. Blueprint Genetics. Comprehensive Epilepsy Panel [21/10/2020]. Available from: https://blueprintgenetics.com/tests/panels/neurology/comprehensive-epilepsy-panel/.
36. Centogene. Epilepsy Panel [21/10/2020]. Available from: https://www.centogene.com/science/centopedia/ngs-panel-genetic-testing-for-generalized-epilepsy-with-febrile-seizures.html
37. Dynacare. Neurosure Epilepsy Gene Panel: Comprehensive (Ontario) [21/10/2020]. Available from: https://www.dynacare.ca/specialpages/secondarynav/find-a-test/nat/neurosure%C2%A0epilepsy%C2%A0gene%C2%A0panel-%C2%A0comprehensive.aspx?sr=ONT&st=.
38. EGL Genetics. Epilepsy and Seizure Disorders Panel: Sequencing and CNV Analysis [21.10.2020]. Available from: https://www.egl-eurofins.com/tests/MEPI1.
39. Invitae. Invitae Epilepsy Panel [21/10/2020]. Available from: https://www.invitae.com/en/physician/tests/03401/.
40. Mayo Clinic Labs. Targeted Genes and Methodology Details for Epilepsy/Seizure Genetic Panels 2019 [21/10/2020]. Available from: https://www.mayocliniclabs.com/it-mmfiles/Targeted_Genes_and_Methodology_Details_for_Epilespy_Genetic_Panels.pdf.
41. Helbig I, Ellis CA. Personalized medicine in genetic epilepsies–possibilities, challenges, and new frontiers. Neuropharmacology. 2020:107970
42. Williams v Quest Diagnostics, Inc.: United States District Court for the District Of South Carolina Columbia Division; 2018. p. 432.
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