Abstract
Dravet syndrome is a severe form of epilepsy characterised by recurrent seizures and cognitive impairment. It is mainly caused by variant in the SCN1A gene in 90% of cases, which codes for the α subunit of the voltage-gated sodium channel. In this study, we present one suspected case of Dravet syndrome in Moroccan child that underwent exome analysis and were confirmed by Sanger sequencing. The variant was identified in the SCN1A gene, and is a new variant that has never been described in the literature. The variant was found de nova in our case, indicating that it was not inherited from the parents. The variant, SCN1A c.965-2A>G p.(?), is located at the splice site and results in an unknown modification of the protein. This variant is considered pathogenic on the basis of previous studies. These results contribute to our knowledge of the SCN1A gene mutations associated with Dravet syndrome and underline the importance of genetic analysis in the diagnosis and confirmation of this disorder. Further studies are needed to better understand the functional consequences of this variant and its implications for therapeutic strategies in Dravet syndrome.
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References
Cardenal-Muñoz E, Auvin S, Villanueva V, Cross JH, Zuberi SM, Lagae L et al (2022) Guidance on Dravet syndrome from infant to adult care: Road map for treatment planning in Europe. Epilepsia Open 7(1):11–26
Bernardina BD, Capovilla G, Gattoni MB, Colamaria V, Bondavalli S, Bureau M (1982) Epilepsie myoclonique grave de la premiere annee. Rev Electroencéphalographie Neurophysiol Clin 12(1):21–25
Connolly MB (2016) Dravet Syndrome: diagnosis and long-term course. Can J Neurol Sci J Can Sci Neurol 43(Suppl 3):S3–8
Lagae L (2021) Dravet syndrome. Curr Opin Neurol 34(2):213–218
Marini C, Scheffer IE, Nabbout R, Suls A, De Jonghe P, Zara F et al (2011) The genetics of Dravet syndrome. Epilepsia 52(s2):24–29
Kalume F, Westenbroek RE, Cheah CS, Yu FH, Oakley JC, Scheuer T et al (2013) Sudden unexpected death in a mouse model of Dravet syndrome. J Clin Invest 123(4):1798–1808
Zuberi SM, Brunklaus A, Birch R, Reavey E, Duncan J, Forbes GH (2011) Genotype–phenotype associations in SCN1A-related epilepsies. Neurology 76(7):594–600
Rampazzo ACM, dos Santos RRP, Maluf FA, Simm RF, Marson FAL, Ortega MM et al (2021) Dravet syndrome and dravet syndrome-like phenotype: a systematic review of the SCN1A and PCDH19 variants. Neurogenetics 22(2):105–115
Wheless JW, Fulton SP, Mudigoudar BD (2020) Dravet Syndrome: a review of current management. Pediatr Neurol 107:28–40
Ding J, Li X, Tian H, Wang L, Guo B, Wang Y et al (2021) SCN1A Mutation—Beyond Dravet Syndrome: a systematic review and narrative synthesis. Front Neurol 12:743726
Rhodes TH, Lossin C, Vanoye CG, Wang DW, George AL (2004) Noninactivating voltage-gated sodium channels in severe myoclonic epilepsy of infancy. Proc Natl Acad Sci 101(30):11147–11152
Lossin C, Rhodes TH, Desai RR, Vanoye CG, Wang D, Carniciu S et al (2003) Epilepsy-Associated Dysfunction in the Voltage-gated Neuronal Sodium Channel SCN1A. J Neurosci 23(36):11289–11295
Fang ZX, Hong SQ, Li TS, Wang J, Xie LL, Han W et al (2019) Genetic and phenotypic characteristics of SCN1A-related epilepsy in Chinese children. NeuroReport 30(9):671–680
Xu C, Zhang Y, Gozal D, Carney P (2021) Channelopathy of Dravet Syndrome and potential neuroprotective effects of Cannabidiol. J Cent Nerv Syst Dis 13:11795735211048045
Brunklaus A, Schorge S, Smith AD, Ghanty I, Stewart K, Gardiner S et al (2020) SCN1A variants from bench to bedside—improved clinical prediction from functional characterization. Hum Mutat 41(2):363–374
Frampton JE, Fenfluramine (2023) A review in Dravet and Lennox-Gastaut syndromes. Drugs 83(10):923–934
Sahli M, Zrhidri A, Elaloui SC, Smaili W, Lyahyai J, Oudghiri FZ et al (2019) Clinical exome sequencing identifies two novel mutations of the SCN1A and SCN2A genes in Moroccan patients with epilepsy: a case series. J Med Case Reports 13(1):266
Shibata A, Kasai M, Terashima H, Hoshino A, Miyagawa T, Kikuchi K et al (2020) Case-control association study of rare nonsynonymous variants of SCN1A and KCNQ2 in acute encephalopathy with biphasic seizures and late reduced diffusion. J Neurol Sci 414:116808
Catterall WA (2000) From ionic currents to Molecular mechanisms: the structure and function of Voltage-gated Sodium channels. Neuron 26(1):13–25
Takayama R, Fujiwara T, Shigematsu H, Imai K, Takahashi Y, Yamakawa K et al (2014) Long-term course of Dravet syndrome: a study from an epilepsy center in Japan. Epilepsia 55(4):528–538
Volkers L, Kahlig KM, Verbeek NE, Das JHG, van Kempen MJA, Stroink H et al (2011) Nav1.1 dysfunction in genetic epilepsy with febrile seizures-plus or dravet syndrome: analysis of Nav1.1 missense mutations in epilepsy. Eur J Neurosci 34(8):1268–1275
Bechi G, Rusconi R, Cestèle S, Striano P, Franceschetti S, Mantegazza M (2015) Rescuable folding defective NaV1.1 (SCN1A) mutants in epilepsy: Properties, occurrence, and novel rescuing strategy with peptides targeted to the endoplasmic reticulum. Neurobiol Dis 75:100–114
Sun Y, Paşca SP, Portmann T, Goold C, Worringer KA, Guan W et al (2016) A deleterious Nav1.1 mutation selectively impairs telencephalic inhibitory neurons derived from Dravet Syndrome patients. eLife 5:e13073
Carvill GL, Engel KL, Ramamurthy A, Cochran JN, Roovers J, Stamberger H et al (2018) Aberrant inclusion of a poison exon causes dravet syndrome and related SCN1A-Associated Genetic epilepsies. Am J Hum Genet 103(6):1022–1029
Martins Custodio H, Clayton LM, Bellampalli R, Pagni S, Silvennoinen K, Caswell R et al (2023) Widespread genomic influences on phenotype in Dravet syndrome, a ‘monogenic’ condition. Brain. ;awad111
Brunklaus A, Brünger T, Feng T, Fons C, Lehikoinen A, Panagiotakaki E et al (2022) The gain of function SCN1A disorder spectrum: novel epilepsy phenotypes and therapeutic implications. Brain 145(11):3816–3831
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All authors contributed to the study conception and design. Manuscript drafting by HE MJ and MA. Article revision by LB. Patient’s clinical assessment conducted by SC and AN. Exome sequencing analysis by NA, JL, and SCE. Sanger sequencing performed by HE and MA. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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The study was conducted following the guidelines and regulations outlined by the relevant ethics committees and institutional review boards. Informed consent was obtained from all participants or their legal guardians prior to sample collection and sequencing.
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El Mouhi, H., Amllal, N., Abbassi, M. et al. Identification of novel and de novo variant in the SCN1A gene confirms Dravet syndrome in Moroccan child: a case report. Mol Biol Rep 51, 233 (2024). https://doi.org/10.1007/s11033-023-09200-y
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DOI: https://doi.org/10.1007/s11033-023-09200-y