{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSCN1A encodes the alpha‐subunit of the voltage‐gated sodium channel Nav1.1, a protein that is essential for the initiation and propagation of action potentials in the central nervous system. In many studies, Nav1.1 has been shown to be preferentially localized at critical neuronal sites—including axon initial segments of inhibitory interneurons—thereby regulating the balance between neuronal excitation and inhibition. Disruptions in this channel underlie a broad spectrum of epileptic syndromes, with mutations in SCN1A representing a predominant genetic determinant in disorders such as Dravet syndrome, generalized epilepsy with febrile seizures plus (GEFS+), and related encephalopathies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nA large body of work has demonstrated that mutations in SCN1A frequently lead to loss-of-function alterations that reduce sodium currents in GABAergic inhibitory neurons—in turn diminishing the ability of these cells to generate high-frequency action potentials. In addition, electrophysiological studies have revealed that certain missense mutations can disturb channel gating by altering activation/inactivation kinetics, promoting partial channel dysfunction or even paradoxical gain-of-function features in select contexts. This altered channel behavior, ranging from persistent noninactivating currents to decreased current densities and aberrant recovery from inactivation, is held responsible for the hyperexcitability observed in various childhood epileptic encephalopathies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "33"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its central role in normal neuronal excitability, SCN1A’s function is intricately modulated by processes such as alternative splicing and interactions with accessory proteins, which can fine-tune channel kinetics and surface expression. These modulatory mechanisms contribute to the variable clinical penetrance observed in conditions ranging from epileptic encephalopathies to familial hemiplegic migraine. Recent advances employing patient-derived neurons and genome-editing techniques have underscored how even partial rescue of channel function can rebalance network excitability, suggesting promising avenues for targeted therapeutic intervention in disorders linked to SCN1A dysfunction."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "34", "end_ref": "49"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ikuo Ogiwara, Hiroyuki Miyamoto, Noriyuki Morita, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Molecular basis of an inherited epilepsy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0896-6273(02)00714-6"}], "href": "https://doi.org/10.1016/s0896-6273(02"}, {"type": "t", "text": "00714-6) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12086636"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12086636"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Christel Depienne, Delphine Bouteiller, Boris Keren, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "A novel SCN1A mutation associated with generalized epilepsy with febrile seizures plus--and prevalence of variants in patients with epilepsy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/319524"}], "href": "https://doi.org/10.1086/319524"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11254445"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11254445"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "R Nabbout, E Gennaro, B Dalla Bernardina, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "De-novo mutations of the sodium channel gene SCN1A in alleged vaccine encephalopathy: a retrospective study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lancet Neurol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/S1474-4422(06)70446-X"}], "href": "https://doi.org/10.1016/S1474-4422(06"}, {"type": "t", "text": "70446-X) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16713920"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16713920"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Goryu Fukuma, Hirokazu Oguni, Yukiyoshi Shirasaka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations of neuronal voltage-gated Na+ channel alpha 1 subunit gene SCN1A in core severe myoclonic epilepsy in infancy (SMEI) and in borderline SMEI (SMEB)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Epilepsia (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.0013-9580.2004.15103.x"}], "href": "https://doi.org/10.1111/j.0013-9580.2004.15103.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14738421"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14738421"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Christoph Lossin, Thomas H Rhodes, Reshma R Desai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epilepsy-associated dysfunction in the voltage-gated neuronal sodium channel SCN1A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2003)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14672992"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14672992"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Lieve Claes, Berten Ceulemans, Dominique Audenaert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "De novo SCN1A mutations are a major cause of severe myoclonic epilepsy of infancy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.10217"}], "href": "https://doi.org/10.1002/humu.10217"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12754708"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12754708"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Massimo Mantegazza, Antonio Gambardella, Raffaella Rusconi, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Sodium channel alpha1-subunit mutations in severe myoclonic epilepsy of infancy and infantile spasms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurology (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1212/01.wnl.0000086379.71183.78"}], "href": "https://doi.org/10.1212/01.wnl.0000086379.71183.78"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14504318"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14504318"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Akshitkumar M Mistry, Christopher H Thompson, Alison R Miller, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "A novel epilepsy mutation in the sodium channel SCN1A identifies a cytoplasmic domain for beta subunit interaction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.2034-04.2004"}], "href": "https://doi.org/10.1523/JNEUROSCI.2034-04.2004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15525788"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15525788"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Dalia Kasperaviciute, Claudia B Catarino, Mar Matarin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/brain/awt233"}], "href": "https://doi.org/10.1093/brain/awt233"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24014518"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24014518"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Carla Marini, Ingrid E Scheffer, Rima Nabbout, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SCN1A duplications and deletions detected in Dravet syndrome: implications for molecular diagnosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Epilepsia (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1528-1167.2009.02013.x"}], "href": "https://doi.org/10.1111/j.1528-1167.2009.02013.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19400878"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19400878"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Michael Steffens, Costin Leu, Ann-Kathrin Ruppert, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2015.11.009"}], "href": "https://doi.org/10.1016/j.neuron.2015.11.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26637798"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26637798"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Christel Depienne, Oriane Trouillard, Isabelle Gourfinkel-An, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mechanisms for variable expressivity of inherited SCN1A mutations causing Dravet syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.2009.074328"}], "href": "https://doi.org/10.1136/jmg.2009.074328"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20522430"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20522430"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "K Kanai, S Hirose, H Oguni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effect of localization of missense mutations in SCN1A on epilepsy phenotype severity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurology (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1212/01.wnl.0000129829.31179.5b"}], "href": "https://doi.org/10.1212/01.wnl.0000129829.31179.5b"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15277629"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15277629"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Berten P G M Ceulemans, Lieve R F Claes, Lieven G Lagae "}, {"type": "b", "children": [{"type": "t", "text": "Clinical correlations of mutations in the SCN1A gene: from febrile seizures to severe myoclonic epilepsy in infancy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pediatr Neurol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.pediatrneurol.2003.10.012"}], "href": "https://doi.org/10.1016/j.pediatrneurol.2003.10.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15087100"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15087100"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Lieve R F Claes, Liesbet Deprez, Arvid Suls, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The SCN1A variant database: a novel research and diagnostic tool."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.21083"}], "href": "https://doi.org/10.1002/humu.21083"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19585586"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19585586"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Yishan Sun, Sergiu P Paşca, Thomas Portmann, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Modulatory proteins can rescue a trafficking defective epileptogenic Nav1.1 Na+ channel mutant."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.3515-07.2007"}], "href": "https://doi.org/10.1523/JNEUROSCI.3515-07.2007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17928445"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17928445"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Sandrine Cestèle, Paolo Scalmani, Raffaella Rusconi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Self-limited hyperexcitability: functional effect of a familial hemiplegic migraine mutation of the Nav1.1 (SCN1A) Na+ channel."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.4453-07.2008"}], "href": "https://doi.org/10.1523/JNEUROSCI.4453-07.2008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18632931"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18632931"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Lynette G Sadleir, Emily I Mountier, Deepak Gill, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Not all "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "SCN1A"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " epileptic encephalopathies are Dravet syndrome: Early profound Thr226Met phenotype."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurology (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1212/WNL.0000000000004331"}], "href": "https://doi.org/10.1212/WNL.0000000000004331"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28794249"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28794249"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Anne M McIntosh, Jacinta McMahon, Leanne M Dibbens, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effects of vaccination on onset and outcome of Dravet syndrome: a retrospective study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lancet Neurol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/S1474-4422(10)70107-1"}], "href": "https://doi.org/10.1016/S1474-4422(10"}, {"type": "t", "text": "70107-1) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20447868"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20447868"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Erin L Heinzen, Woohyun Yoon, Sarah K Tate, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nova2 interacts with a cis-acting polymorphism to influence the proportions of drug-responsive splice variants of SCN1A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/516650"}], "href": "https://doi.org/10.1086/516650"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17436242"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17436242"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Elena Gennaro, Filippo M Santorelli, Enrico Bertini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Somatic and germline mosaicisms in severe myoclonic epilepsy of infancy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2005.12.209"}], "href": "https://doi.org/10.1016/j.bbrc.2005.12.209"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16430863"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16430863"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Kristopher M Kahlig, Thomas H Rhodes, Michael Pusch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Divergent sodium channel defects in familial hemiplegic migraine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0711717105"}], "href": "https://doi.org/10.1073/pnas.0711717105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18621678"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18621678"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "B de Vries, T Freilinger, K R J Vanmolkot, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Systematic analysis of three FHM genes in 39 sporadic patients with hemiplegic migraine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurology (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1212/01.wnl.0000295670.01629.5a"}], "href": "https://doi.org/10.1212/01.wnl.0000295670.01629.5a"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18056581"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18056581"}]}, {"type": "r", "ref": 43, "children": [{"type": "t", "text": "Allan Bayat, Helle Hjalgrim, Rikke S Møller "}, {"type": "b", "children": [{"type": "t", "text": "The incidence of SCN1A-related Dravet syndrome in Denmark is 1:22,000: a population-based study from 2004 to 2009."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Epilepsia (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/epi.12927"}], "href": "https://doi.org/10.1111/epi.12927"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25778844"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25778844"}]}, {"type": "r", "ref": 44, "children": [{"type": "t", "text": "Lata Vadlamudi, Leanne M Dibbens, Kate M Lawrence, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Timing of de novo mutagenesis--a twin study of sodium-channel mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "N Engl J Med (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1056/NEJMoa0910752"}], "href": "https://doi.org/10.1056/NEJMoa0910752"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20879882"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20879882"}]}, {"type": "r", "ref": 45, "children": [{"type": "t", "text": "Tomohide Abe, Takayuki Seo, Takateru Ishitsu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association between SCN1A polymorphism and carbamazepine-resistant epilepsy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Clin Pharmacol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2125.2008.03203.x"}], "href": "https://doi.org/10.1111/j.1365-2125.2008.03203.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18489610"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18489610"}]}, {"type": "r", "ref": 46, "children": [{"type": "t", "text": "Sandrine Cestèle, Emanuele Schiavon, Raffaella Rusconi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nonfunctional NaV1.1 familial hemiplegic migraine mutant transformed into gain of function by partial rescue of folding defects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1309827110"}], "href": "https://doi.org/10.1073/pnas.1309827110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24101488"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24101488"}]}, {"type": "r", "ref": 47, "children": [{"type": "t", "text": "Alex C Bender, Richard P Morse, Rod C Scott, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SCN1A mutations in Dravet syndrome: impact of interneuron dysfunction on neural networks and cognitive outcome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Epilepsy Behav (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yebeh.2011.11.022"}], "href": "https://doi.org/10.1016/j.yebeh.2011.11.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22341965"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22341965"}]}, {"type": "r", "ref": 48, "children": [{"type": "t", "text": "J Liu, C Gao, W Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CRISPR/Cas9 facilitates investigation of neural circuit disease using human iPSCs: mechanism of epilepsy caused by an SCN1A loss-of-function mutation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Transl Psychiatry (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/tp.2015.203"}], "href": "https://doi.org/10.1038/tp.2015.203"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26731440"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26731440"}]}, {"type": "r", "ref": 49, "children": [{"type": "t", "text": "Kaate R J Vanmolkot, Elena Babini, Boukje de Vries, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The novel p.L1649Q mutation in the SCN1A epilepsy gene is associated with familial hemiplegic migraine: genetic and functional studies. Mutation in brief #957. Online."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.9486"}], "href": "https://doi.org/10.1002/humu.9486"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17397047"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17397047"}]}]}]}