No retraction, correction or concern found when last checked on Oct 26, 2026.

Epilepsy-Related Voltage-Gated Sodium Channelopathies: A Review

Luis Felipe Santos Menezes, Elias Ferreira Sabiá Júnior, Diogo Vieira Tibery and 2 more

Frontiers in Pharmacology · 2020 · Review · CC BY

doi:10.3389/fphar.2020.01276

Abstract

Epilepsy is a disease characterized by abnormal brain activity and a predisposition to generate epileptic seizures, leading to neurobiological, cognitive, psychological, social, and economic impacts for the patient. There are several known causes for epilepsy; one of them is the malfunction of ion channels, resulting from mutations. Voltage-gated sodium channels (NaV) play an essential role in the generation and propagation of action potential, and malfunction caused by mutations can induce irregular neuronal activity. That said, several genetic variations in NaV channels have been described and associated with epilepsy. These mutations can affect channel kinetics, modifying channel activation, inactivation, recovery from inactivation, and/or the current window. Among the NaV subtypes related to epilepsy, NaV1.1 is doubtless the most relevant, with more than 1500 mutations described. Truncation and missense mutations are the most observed alterations. In addition, several studies have already related mutated NaV channels with the electrophysiological functioning of the channel, aiming to correlate with the epilepsy phenotype. The present review provides an overview of studies on epilepsy-associated mutated human NaV1.1, NaV1.2, NaV1.3, NaV1.6, and NaV1.7.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 26, 2026. Paragraph numbers are ours, so an answer can point at one.

Introduction

1Epilepsy is a disease known worldwide, affecting around 70 million people in the world. It has been considered a disease and no longer a disorder or a family of disorders since 2014 by International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsy is conceptually defined as a disease in which an individual has at least two unprovoked or reflex seizures in a period greater than 24 h apart, one unprovoked or reflex seizure and a probability of having another seizure similar to the general recurrence risk after two unprovoked seizures (greater than or equal to 60%) over the next ten years or an epilepsy syndrome.

2When abnormal brain activity begins in one or more identified regions, epilepsy is called focal, whereas, when it occurs in both hemispheres with a wide distribution, it is called generalized. Finally, when it cannot be classified as either focal or generalized, it is called unknown.

3Epilepsy can affect anyone, regardless of gender, age, and income levels. Understanding the etiology of epilepsy is crucial for clinical management of patients and for conducting neurobiological research that will direct future therapies. The ILAE Task Force has defined six etiologic categories; they are not hierarchical and more than one might often apply (structural, genetic, infectious, metabolic, immune, and unknown).

4Among those genetically caused, it is possible to identify several epilepsy-related genes. For example, voltage-gated potassium channel, voltage-gated calcium channel and voltage-gated chloride channel genes, GABA receptors, nicotinic acetylcholine receptors, polymerase (DNA) Gamma genes and voltage-gated sodium channel genes.

5Voltage-gated sodium channels (NaV) can be found mainly in the central nervous system (CNS), peripheral nervous systems (PNS), skeletal, and cardiac muscles. NaVs are distributed throughout the body and play an important role in the generation and propagation of action potential. Structurally, NaVs are composed by an α subunit organized in four homologous ligated domains (DI-DIV), each domain composed by six transmembrane segments (S1-S6), and one or more β subunits associated by non-covalent interactions or disulfide bond. The domains of an α subunit present a high degree of conservation with each other, presenting the region known as the voltage sensor domains (VSD) located in transmembranes S1-S4, especially S4 helix, which contains positively charged residues, and the pore-forming (PM) domain located in S5-S6 segments, structuring a four VSD around a central pore.

6The S4 helix of DI, DII, and DIII domains moves faster than the S4 helix of DIV during membrane depolarization, and this asynchronous movement is an essential feature in the steady activation voltage-dependent process, which provokes movement of S4-S5 intracellular links followed by the displacement of the S6 segments to initiate Na+ influx. The movement of the S4 helix of DIV initiates the process of fast inactivation, since the movement of the voltage sensor in domain DIV is associated with the displacement of an intracellular loop between DIII and DIV within an IFM (isoleucine, phenylalanine, and methionine) motif that binds intracellular to PM and terminate Na+ influx. A second type of reversible inactivation occurs after repetitive or prolonged stimulation and results in steady-state inactivation whose asymmetric movement of S6 segments collapses the pore. Consequently, electrophysiological changes such as increased current density, shifting steady-state activation, and inactivation to negative and positive values, respectively, enhanced persistent current, accelerated recovery from inactivation, and delayed fast inactivation can cause gain-of-function (GoF) in the channel. Also, decreased current density, positive shift in steady-state activation, negative shift in steady-state inactivation, and slower recovery from inactivation can cause loss-of-function (LoF).

7Currently, there are nine different alpha subtypes of NaVs (NaV1.1-NaV1.9), and mutations in these channels can cause diseases known as channelopathies. NaV1.1 (SCN1A), NaV1.2 (SCN2A), NaV1.3 (SCN3A), NaV1.6 (SCN8A) and NaV1.7 (SCN9A) are genes whose mutations are related to epilepsy. So far, there is no correlation of mutations in NaV1.4 (SCN4A), NaV1.5 (SCN5A), NaV1.8 (SCN10A), and NaV1.9 (SCN11A) with epilepsy, which is to be expected, since these channels are mainly expressed in skeletal muscles, cardiac tissues, dorsal root ganglia, trigeminal sensory neurons, nociceptive neurons of the dorsal root and trigeminal ganglia, respectively. Both α and β subunits (SCN1B) have been reported as the cause of epilepsy phenotype.

8NaV channels rank amongst the 2% most conserved proteins in the human genome, with an extremely low rate of coding variation, accounting for nearly 5% of known epileptic encephalopathies. Pathogenic mutated residues are situated in the highly evolutionarily conserved portions of the channel: transmembrane segments, intracellular inactivation gate loop, and the proximal 2/3 of the C-terminal domain. The final 1/3 portion of the C-terminal and cytoplasmic interdomain loops 1 and 2 are less conserved. The proximal 2/3 of the C-terminal are involved in the interaction of several binding sites for proteins and accessory molecules, like beta subunits β1 and β3, fibroblast growth factors (molecules implicated in neural development), calmodulin (regulatory protein in neuronal function and hyperexcitability) and G protein. Moreover, the C-terminal has been shown to interact with the inactivated channel via ionic interaction between its positively charged residues and negatively charged residues at the inactivation gate. A shift in any of the charges can brake electrostatic interaction and affect normal channel inactivation.

9The N-terminal region seems to play a more important role on protein trafficking than on channel activity. This domain interacts with the light chain of microtubule-associated protein MAP1B, facilitating the traffic of the NaV channel to the neuronal cell surface. In addition, mutation in the N-terminal leads to protein retention in the endoplasmic reticulum.

10Newer genomic approaches, especially next generation sequencing (NGS), improve the rate and reduce the costs associated with genetic epilepsy diagnosis, since traditional cytogenetic and microarray-based tests are lengthy, expensive, and diagnostic yield is incredibly low. The use of gene panels and whole-exome sequencing (WES) provides a powerful tool to change the paradigm of genetic epilepsy diagnosis. These techniques have been widely used to elucidate suspected inherited neurological diseases in the last years, contributing to dramatically increase the number of patients diagnosed with genetic epilepsy. Both mendelian and de novo genetic epilepsy can be detected with these methods, but doubtless, de novo mutations are the most prevalent mutations related to epilepsy-related voltage-gated sodium channel mutations.

11Gene therapy is promising as an effective approach to treat genetic diseases. Personalized epilepsy therapies are in development and have shown promising results, ranging from antisense oligonucleotides and small peptides to modulation of gene expression through epigenetics. Even eating habits may be related to an improvement in the patient's clinical condition. Ketogenic diet has been described as an effective treatment in epilepsy. Moreover, the combination of traditional antiepileptic drugs with new compounds displayed a synergic and improved efficacy, since these molecules do not compete for the same interaction site. Each specific epilepsy-related NaV isoform will be presented and discussed in detail in the following sections.

NaV1.1

12The SCN1A gene encodes for the α subunit NaV1.1, and is allocated at the 2q24.3 chromosome between 165,984,641 and 166,149,161 base pairs, same gene cluster of SCN2A-SCN3A genes, being the most frequent target of mutation in genetic epilepsy syndromes (OMIM#182389). NaV1.1 is widely expressed in the CNS, predominant in inhibitory GABAergic interneurons, regulating neuronal excitability, and the reduction of its activity is one of the factors that cause epileptic diseases due to imbalance between inhibition and excitation.

13Epilepsy syndromes, such as generalized epilepsy with febrile seizures plus (GEFS+; Online Mendelian Inheritance in Man [OMIM] #604233), severe myoclonic epilepsy (SME) and SMEI, also known as Dravet syndrome (OMIM #607208), are associated with mutations in the SCN1A gene.

14In the SCN1A mutation database (http://www.caae.org.cn/gzneurosci/scn1adatabase/data), among 1727 mutations described for the SCN1A gene, 1528 are related to epileptic diseases ( Table 1 and for the full description of mutations in the SCN1A gene, see Supplementary Table S1 ). Among the epilepsy-related mutations, 945 are related to severe myoclonic epilepsy of infancy (SMEI), 263 are related to severe myoclonic epilepsy (SME), 151 are related to severe myoclonic epilepsy borderline (SMEB), 18 are related to partial epilepsy (PE), 31 are related to partial epilepsy and febrile seizures plus (PEFS +), 8 are related to generalized epilepsy (GE), and 55 are related to generalized epilepsy with febrile seizures plus (GEFS +).

15Mutations in the NaV1.1 channel are described in almost all regions of the protein and may cause GoF or LoF. Among the 52 mutations in SCN1A related to epilepsy with functional studies, 35 mutations (67.30%) exclusively display characteristics of LoF, 6 mutations (11.53%) display characteristics unique to GoF, and 11 mutations (21,15%) display characteristics of GoF+LoF, whereas, in GoF+LoF mutations, the main characteristic that gives GoF features is enhanced persistent current, present in 10 out of the 11 GoF+LoF mutations listed ( Tables 1 and S1 ).

16Due to the role of the NaV1.1 channels in the regulation of electrical excitability by the inhibitory interneurons, prescription of AEDs non-selective sodium channel blockers (SCB) for SMEI or GEFS + syndromes is contraindicated, for it may aggravate crises due to the enhanced suppress status of the NaV1.1 channels. The first-line drug-based therapy for SCN1A epilepsy diseases is the enhancement of postsynaptic GABAergic transmission with allosteric activation of GABAA receptors as target by Clobazam and/or an increase in GABA concentration in synaptic cleft resulting from increased GABA production and decreased GABA degradation as target by Valproic acid. Antisense nucleotides (ASO) therapy to increase mRNA of SCN1A for NaV1.1 channel expression in normal levels is a promising strategy for genetic disorders involving haploinsufficiency. Drug-resistant Dravet syndrome cases may thrive on alternative therapeutic strategies based on ketogenic diets. A recent study with 20 patients with medically intractable Dravet syndrome caused by missense, non-sense, insertion, deletions and splicing mutations presents efficacy during three months of treatment in 17 patients, decreasing seizure frequency in more than 50%. Besisdes that, Epidiolex is an FDA approved CBD-based drug approved in June 2018 for the treatment of severe forms of epilepsy, as Dravet and Lennox-Gastaut syndromes (U.S. Food and Drug Administration [website]., 2018). Clinical trials using CBD in DS and LGS shown reduced frequency of seizures in monthly average. Voltage-gated sodium channel are inhibit by CBD in low micromolar concentrations, IC50 between 1.9 and 3.8 μM, NaV1.4 and NaV1.1 being the most sensitive channels to CBD, 1.9 and 2.0 μM respectively, probably the mechanism of action is reducing channel availability due shift to more hyperpolarized potential in steady-state inactivation (Ghovanloo et al., 2019).

NaV1.2

17NaV1.2 is encoded by the SCN2A gene. It is located on chromosome 2q24.3 and expressed in the CNS, especially in excitatory neurons and glutamatergic neurons, unlike the NaV1.1 channel, which is highly expressed in the GABAergic interneurons.

18More than 100 mutations have already been described for this gene, with approximately 300 patients studied yet ( Table 2 ). The most common diseases related with SCN2A mutation are West syndrome (WS; OMIM #308350), epilepsy of infancy with migrating focal seizures (EIMFS; OMIM #616645), and benign familial neonatal-infantile seizures (BFNIS; OMIM #607745). Although epilepsy-related mutations are present throughout the channel, several hotspots such as the ion selectivity filter, the voltage-sensing domain, the intracellular N-terminal, and the C-terminal domain can be highlighted.

19NaV1.2 channels are expressed in the excitatory neurons; therefore, GoF mutations are related to epilepsy because it causes neuronal hyperexcitability. On the other hand, LoF mutations are related to autism and intellectual disability phenotype. Nevertheless, some studies have already related loss of function to epilepsy, as described by with R1312T mutation. Normally, LoF SCN2A gene mutations for epilepsy are related to late-onset epilepsy; however, the mechanism of action is unclear.

20In some cases, NaV1.2 seizures are not controlled not even by various antiepileptic drugs, as with the patient described by. The proband, even after being treated with oxcarbazepine (OXC), valproic acid, topiramate, sulthiame, phenytoin, among other drugs, kept on having seizures. Furthermore, the SCB drugs can assist the patient during the treatment as described by. The patient had seizures controlled after administration of phenytoin. In addition, cite benefits treatments using SCB such as carbamazepine, mexiletine, oxcarbazepine, phenytoin, lidocaine, and lamotrigine for patients with early onset epilepsies. Besides, Peters and colleagues studied a substance commercially used as an antianginal drug (human heart) called ranolazine that has been shown to affect NaV1.2 channels, reducing macroscopic currents and delaying the recovery of fast and slow inactivation of the NaV1.2 channel, consequently with more future studies ranolazine could be a efficacious therapy for epilepsy.

21Drugs can be important to modulate channel kinetics for both GoF and LoF, but some precautions must be observed. For example, the degree of conservation between subtypes, such as NaV1.2 and other sodium channels as NaV1.5 and the excessive decrease in channel function or the excessive increase in function obtained by the drug.

22Organizations like the FamilieSCN2A Foundation (www.scn2a.org) might be essential in the search for new treatments. Understanding the genotype-phenotype of gain and loss of function is essential because science-patient relationship may be helpful in the search for new therapies.

NaV1.3

23SCN3A is a gene that encodes for type 3 voltage-gated Na+ channel α subunit, the NaV1.3, located on human chromosome 2q24, in a cluster with SCN1A and SCN2A. NaV1.3 is expressed predominantly in the CNS during embryonic and neonatal development, being extremely low or sometimes undetectable in postnatal individuals. Subsequently, during infancy, it is gradually replaced by increased expression of the NaV1.1 isoform. On the other hand, studies regarding nervous system injury and neuropathic pain showed an increasing presence of NaV1.3 channels in affected tissues, suggesting a pivotal hole of these transmembrane proteins in these processes and diseases. For the reasons mentioned above, in the last decades, NaV1.3-associated pathogenesis has been restricted to pain. Recently, a genetic linkage between NaV1.3 mutated variants and epilepsy has been suggested, especially in cryptogenic epilepsy cases (OMIM#182391).

24K354Q was the first described NaV1.3 epilepsy-related mutation that revealed harmful electrophysiological alterations. In fact, mutations can change many functional characteristics of NaV1.3 affecting biophysical properties differently; however, these changes result predominantly in neuronal hyper-responsiveness ( Table 3 ). Previous reports correlate heterozygous variants in SCN3A in association with moderate forms of epilepsy, while homozygosis is related with severe cognitive damage and premature mortality, resulting in a broad range of epileptic phenotypes.

25Different hereditary mutations on NaV1.3 have been reported to date in patients with epilepsy. In general, the biophysical characterization of these mutations reveals GoF, only one mutation (N302S) is related with LoF, but both GoF and LoF may lead to an increased seizure susceptibility.

26Moreover, several de novo mutations in SCN3A have been described in the last three years, related with severe infantile neurological dysfunctions and cognitive impairments. These mutations may alter the functionality of NaV1.3 channels, neurons organization, migration, and proliferation during the embryonic development. Epileptic encephalopathy and polymicrogyria are the main features related with these pathogenic variants, and, so far, polymicrogyria was not reported in other channelopathies, being an exclusive characteristic of SCN3A mutants.

27There is a lack of clinical data on SCN3A-related epilepsies, especially regarding treatment and the use of specific medication. However, in vitro studies reported that mutations related with GoF effect respond favorably to treatment using SCB, like phenytoin, carbamazepine, lacosamide, and topiramate. The anticonvulsant valproic acid represents a novel and promising epigenetic therapeutic approach. The compound modulates the SCN3A gene through methylation, downregulating the expression of NaV1.3 and, consequently, decreasing biophysical alterations in the channel.

NaV1.6

28The SCN8A gene encodes for type 8 voltage-gated Na+ channel α subunit, the NaV1.6, located in chromosome 12q13.13. The first case of SCN8A pathogenic variant associated with epilepsy was reported eight years ago. Thereafter, due to advances in genome sequencing technology, especially the WES, the number of epilepsy diagnosis associated with NaV1.6 mutations has increased significantly (OMIM #600702), with more than 300 patients diagnosed with SCN8A epilepsy mutations and nearly 200 different putative spots of mutations described, totaling over 100 published reports ( Table 4 ). A website developed especially to present SCN8A epilepsy and related diseases (www.scn8a.net) was created to provide information to families, clinicians, and researchers, gathering news and recent publications on the subject in a private forum for family interaction, to answer questions, strengthening the ties between the community and the researchers.

29NaV1.6 is expressed since prenatal, during fetal development. Shortly after birth, expression begins to increase, reaching maximum levels during the first years of life. This channel is widely expressed in the nodes of Ranvier of myelinated axons and in the distal part of the axon initial segments (AIS), although they are also ubiquitously present throughout the central and peripheral nervous systems, in both excitatory and inhibitory neurons. For these reasons, NaV1.6 is one of the most common subtype of voltage-gated sodium channels found in the central nervous system. In humans, the distal AIS is the specialized membrane region in neurons where action potentials are triggered. Overexpression of Nav1.6 in the AIS has been shown to cause an increase in spontaneous and repetitive firing, a possible explanation for why SCN8A mutations in epilepsy patients are predominantly GoF and affect the action potential threshold. On the other hand, the functional importance of Nav1.6 in inhibitory interneurons is not clear yet, but evidence indicates a role for Nav1.6 in establishing synaptic inhibition in the thalamic network, supporting the LoF results caused by missense mutations in the mature protein. These attributes lead to different network effects in distinct nervous system circuits. Mutations in SCN8A are associated with early-infantile epileptic encephalopathy type 13 (EIEE13; OMIM #614558), a phenotypically heterogeneous early onset epilepsy, with seizure onset happening before 18 months of age. Patients typically develop intellectual disability, developmental delay, and movement disorders. Co-occurrence of autism spectrum disorders, severe juvenile osteoporosis, bradyarrhythmia, cortical visual impairment, and gastrointestinal disorders have been reported in rare cases. Sudden unexpected death in epilepsy (SUDEP) has also been linked to SCN8A mutations, described as the most common cause of death in epilepsy patients. Reports have suggested that patients with SCN8A-related epilepsy have increased risk of SUDEP, ranging from 1% to 10%. One possible correlation of SUDEP with SCN8A-related epilepsy is the presence of NaV1.6 in heart muscles and tissues, being broadly expressed within ventricular myocytes. Single mutations may affect heart function, causing failure of the cardiorespiratory system and, consequently, death. Most recently, few cases of SCN8A-related epilepsies with “milder” phenotype were associated with benign familial infantile seizures-5 (BFIS5; OMIM #617080).

30An increase in new described variants made some mutation patterns visible. Wagnon and co-workers observed numerous cases of the same epiletogenic mutation, and suggested that CpG dinucleotides are mutation hotspots that, through enzymatic processing and epigenetic methylation, can convert cytosine to thymine, such as arginine residues 1617 and 1872. The prominent number of new variant cases in Arg850 indicates this residue as a new hotspot, since the arginine codon holds a CpG dinucleotide. In addition to these mutation hotspots, residues I763, I1327, G1475, A1650, and N1877 do not present CpG dinucleotides in their codon; however, they can be considered recurrent mutations in view of its high repetition cases in literature ( Table 4 ).

31The mutation at position c.- 8A>G produces a pathogenic variant, despite not being inside the gene, or promoter regions, transcriptional and translational sites. This mutation was detected in an untranslated region outside of the Kozak consensus sequence. Its role in SCN8A-related epilepsy is still unclear; however, it may change RNA stability, modulate transcriptional factors and promoters, modify the initiation of translation, or work as an enhancer or silencer in the splicing pattern. For all the reasons mentioned above, Nav1.6 variants are predominantly harmful, and the same mutation can lead to different phenotypes, hampering the correlation of genotypes with phenotypes.

32SCN8A mutations can be both GoF and LoF, which will likely require different approaches and targets. Even in patients with the same SCN8A mutation, the response to the same drug treatment can differ. Surprisingly, most SCN8A-related epilepsies respond favorably to channel blockers. Phenytoin and lacosamide are SBCs widely used in SCN8A mutations with GoF effect, while carbamazepine exhibited positive seizure control in a patient with NaV 1.6 mutation and LoF effect.. Phenytoin demonstrated effectiveness in decreasing seizure episodes in several patients with SCN8A-related epilepsies, however, side effects during prolonged use are very common. A recent study of a DS model using zebrafish demonstrated the use of the channel blocking compound MV1312, which is 5–6 fold selectivity of NaV1.6 over NaV1.1–1.7, reduced burst movement phenotype and the number of epileptiform events, activity similar to that described with the use of a selective NaV1.1 activator AA43279. Selective Nav1.6 blockers may represent a new therapeutic strategy for DS patients. In addition, two precise and promising drugs have been described recently: XEN901 and GS967. XEN901 is an arylsulfonamide highly selective and potent NaV1.6 inhibitor that binds specifically in voltage sensor domain IV, avoiding recovery from inactivation. GS967 is a NaV1.6 modulator that inhibits the persistent sodium current and exhibits a protective effect.

NaV1.7

33The SCN9A gene encodes for the NaV1.7 channel, located in chromosome 2q24. NaV1.7 is expressed preferably in the PNS, but it is also expressed in the CNS. Consequently, mutations in this channel are generally related to pain disorders; however, current studies have described a correlation between epilepsy and this channel (OMIM #603415).

34Pain disorder mutations with GoF are related with diseases such as erythromelalgia (EMI), small-fiber neuropathy (SFN) and paroxysmal extreme pain disorder (PEPD), and mutations with LoF are related with congenital insensitivity to pain (CIP). Epilepsy studies such as showed mutations with GoF phenotype: W1150R, N641Y, and K655R mutations ( Table 5 ). Being that, after treatment with OXC (120 µmol/L), N641Y and K655R reduced sodium current and decreased the opening time of the channel, while W1150R did not alter that. However, in a study conducted by, one of the patients presented generalized tonic-clonic seizure with fever, treated with sodium valproic acid, and a LoF mutation I1901fs was observed ( Table 5 ).

35Variants of NaV1.7 have been related with febrile seizure or GEFS+ and even as asymptomatic. However, SCN9A can act as a putative modifier of NaV1.1 gene; consequently, it can elevate the severity of patients’ phenotype (; Parihar and Ganesh, 2013). Some NaV1.7 mutations could probably contribute to generate a genetic susceptibility to a known epilepsy disease called Dravet syndrome, in a multifactorial way, as a modifier gene. That said, some rare cases of DS found in patients can be understood. For example, even parents with mild phenotype had children with severe cases.

Conclusion and Future Perspectives

36The past two decades have enabled remarkable progress in understanding monogenic epilepsies. NaV-related epilepsies are diseases of phenotypic heterogeneity, since sodium channels are found in both the CNS and the PNS, but with different expression ranges. The lack of a clear genotype-phenotype correlation to help guide patient counseling and management by healthcare professionals makes it very complex, and often expensive, to determine a correct diagnosis. Consequently, identify the monogenic mutation in individual patients with epilepsy is important not only for diagnosis and prognosis, but also for a correct treatment approach.

37Susceptibility to specific treatments may be different depending on the disease’s features, diverging even in patients who share the same phenotype and/or mutation. The use of innovative tools that facilitate and prevent diagnostic delay in patients with epilepsy of unknown etiology onset is crucial. WES has proved to be a valuable tool to circumvent the lack of an accurate and fast diagnosis to epilepsies caused by monogenic mutation, and also cheapen and drastically anticipate diagnosis. This genetic diagnostic tool may reduce traditional investigation costs by 55 to 70%, besides avoiding further pre-surgical evaluation and epilepsy surgery. In addition to the financial impact, it can anticipate diagnosis from nearly 3.5 years to 21 days, optimizing management and health care support.

38Effective and safe drugs for the treatment of monogenic epilepsy are still an unmet clinical need. The drugs currently available in the pharmaceutical market are only palliative methods for a temporary control of the disease symptoms, and few patients will benefit from the existing pharmacotherapy, since a great number of patients treated with antiepileptic channel blockers showed no improvement in clinical conditions. Also, most treated patients exhibited manifold side effects, and the prolonged use of these medications proved to be harmful. Several examples of novel and promising candidate compounds to be used in personalized medicine, such as precision therapies, have been suggested. A previously study demonstrated that CBD at 1μM inhibit preferably resurgent currents than transient current in Nav1.6 WT and also inhibit peak resurgent current in Nav1.6 mutant N1768D, with less effect in current density and without alters voltage dependence of activation Possibly the modulation of CBD over mutations in SCN8A that promotes a phenotype with increased resurgent currents would cause a reduction in the causative excitability of epileptic seizures. CBD also showed its ability to preferential inhibit resurgent currents in the NaV1.2 channel. Due the role of Nav1.2 and Nav1.6 in excitatory neurons, preferentially inhibition in resurgent currents by CBD could possibly reduce the excitability in that subset of neurons and decrease the frequency of seizures by a change in threshold of activation and repetitive fire. Peptides derived from scorpion and spider venom are well known modulator tools in neuroscience and showed specific capacity to regulate most NaV subtypes related with monogenic epilepsy, unlike the available promiscuous drugs that generally interact with any NaV channel isoform. Bioengineering tools, like antisense oligonucleotides capable to regulate NaV1.1 channels expression, and the peptide Hm1, that modulates the function of this subtype of sodium channel, are some innovative treatment examples.

39However, there is still a long path toward the development of efficacious treatments for NaV-related epilepsies. Recent studies offered a better understanding of the complexity of the phenotypic and genetic spectrum, which has only just begun to be elucidated. Biomolecular diagnostic tools will drastically reduce the developmental and cognitive effects caused by misdiagnosis and late diagnosis, and maybe, in the upcoming years, the treatment for inherited NaV-related epilepsies will be conducted ideally in utero, during the prenatal stage. Moreover, further functional studies, with greater cohorts of patients, represent an urgent medical need for a better understanding of the correlations between genotype and clinical symptoms, as well as the different NaV-related epilepsies mechanisms. These studies will improve clinical efficacy and promote safety diagnostic strategies, as well as develop prognosis prediction in the near future.

Author Contributions

40All authors made an intellectual and direct contribution for this article and approved it for publication.

Funding

41This study was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) [407625/2013-5] and the Fundação de Apoio à Pesquisa do Distrito Federal (FAPDF) [grants 193.001.202/2016 and 00193.0000109/2019-17].

Conflict of Interest

42The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References 352

1.
Abdelsayed M. Sokolov S. (2013 ). Voltage-gated sodium channels. Channels 7, 146–152.
Not in our library10.4161/chan.24380
2.
Ahern C. A. Payandeh J. Bosmans F. Chanda B. (2016 ). The hitchhiker’s guide to the voltage-gated sodium channel galaxy. J. Gen. Physiol. 147, 1–24.
Not in our library10.1085/jgp.201511492
3.
Allen A. S. Berkovic S. F. Cossette P. Delanty N. Dlugos D. Eichler E. E. (2013 ). De novo mutations in epileptic encephalopathies. Nature 501, 217–221.
Not in our library10.1038/nature12439
4.
Allen N. M. Conroy J. Shahwan A. Lynch B. Correa R. G. Pena S. D. J. (2016 ). Unexplained early onset epileptic encephalopathy: Exome screening and phenotype expansion. Epilepsia 57, e12–e17.
Not in our library10.1111/epi.13250
5.
Anand G. Collett-White F. Orsini A. Thomas S. Jayapal S. Trump N. (2016 ). Autosomal dominant SCN8A mutation with an unusually mild phenotype. Eur. J. Paediatr. Neurol. 20, 761–765.
Not in our library10.1016/j.ejpn.2016.04.015
6.
Annesi G. Gambardella A. Carrideo S. Incorpora G. Labate A. Pasqua A. A. (2003 ). Two Novel SCN1A Missense Mutations in Generalized Epilepsy with Febrile Seizures Plus. Epilepsia 44, 1257–1258.
Not in our library10.1046/j.1528-1157.2003.22503.x
7.
Arafat A. Jing P. Ma Y. Pu M. Nan G. Fang H. (2017 ). Unexplained Early Infantile Epileptic Encephalopathy in Han Chinese Children: Next-Generation Sequencing and Phenotype Enriching. Sci. Rep. 7:46227.
Not in our library10.1038/srep46227
8.
Atanasoska M. Vazharova R. Ivanov I. Balabanski L. Andonova S. Ivanov S. (2018 ). SCN8A p.Arg1872Gln mutation in early infantile epileptic encephalopathy type 13: Review and case report. Biotechnol. Biotechnol. Equip. 32, 1345–1351.
Not in our library10.1080/13102818.2018.1532815
9.
Bähler M. Rhoads A. (2002 ). Calmodulin signaling via the IQ motif. FEBS Lett. 513, 107–113.
Not in our library10.1016/s0014-5793(01)03239-2
10.
Baasch A. L. Hüning I. Gilissen C. Klepper J. Veltman J. A. Gillessen-Kaesbach G. (2014 ). Exome sequencing identifies a de novo SCN2A mutation in a patient with intractable seizures, severe intellectual disability, optic atrophy, muscular hypotonia, and brain abnormalities. Epilepsia 55, e25–e29.
Not in our library10.1111/epi.12554
11.
Bagnasco I. Dassi P. Blé R. Vigliano P. (2018 ). A relatively mild phenotype associated with mutation of SCN8A. Seizure 56, 47–49.
Not in our library10.1016/j.seizure.2018.01.021
12.
Baker E. M. Thompson C. H. Hawkins N. A. Wagnon J. L. Wengert E. R. Patel M. K. (2018 ). The novel sodium channel modulator GS-458967 (GS967) is an effective treatment in a mouse model of SCN8A encephalopathy. Epilepsia 59, 1166–1176.
Not in our library10.1111/epi.14196
13.
Balciuniene J. DeChene E. T. Akgumus G. Romasko E. J. Cao K. Dubbs H. A. (2019 ). Use of a Dynamic Genetic Testing Approach for Childhood-Onset Epilepsy. JAMA Netw. Open 2, e192129.
Not in our library10.1001/jamanetworkopen.2019.2129
14.
Barba C. Parrini E. Coras R. Galuppi A. Craiu D. Kluger G. (2014 ). Co-occurring malformations of cortical development and SCN1A gene mutations. Epilepsia 55, 1009–1019.
Not in our library10.1111/epi.12658
15.
Baroni D. Picco C. Moran O. (2018 ). A mutation of SCN1B associated with GEFS+ causes functional and maturation defects of the voltage-dependent sodium channel. Hum. Mutat. 39, 1402–1415.
Not in our library10.1002/humu.23589
16.
Bartnik M. Chun-Hui Tsai A. Xia Z. Cheung S. Stankiewicz P. (2011 ). Disruption of the SCN2A and SCN3A genes in a patient with mental retardation, neurobehavioral and psychiatric abnormalities, and a history of infantile seizures. Clin. Genet. 80, 191–195.
Not in our library10.1111/j.1399-0004.2010.01526.x
17.
Baumer F. M. Peters J. M. El Achkar C. M. Pearl P. L. (2015 ). SCN2A-Related Early-Onset Epileptic Encephalopathy Responsive to Phenobarbital. J. Pediatr. Epilepsy 05, 042–046.
Not in our library10.1055/s-0035-1567853
18.
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.
Not in our library10.1016/j.nbd.2014.12.028
19.
Bennett C. A. Petrovski S. Oliver K. L. Berkovic S. F. (2017 ). ExACtly zero or once. Neurol. Genet. 3, e163.
Not in our library10.1212/nxg.0000000000000163
20.
Ben-Shalom R. Keeshen C. M. Berrios K. N. An J. Y. Sanders S. J. Bender K. J. (2017 ). Opposing Effects on NaV1.2 Function Underlie Differences Between SCN2A Variants Observed in Individuals With Autism Spectrum Disorder or Infantile Seizures. Biol. Psychiatry 82, 224–232.
Not in our library10.1016/j.biopsych.2017.01.009
21.
Berecki G. Howell K. B. Deerasooriya Y. H. Cilio M. R. Oliva M. K. Kaplan D. (2018 ). Dynamic action potential clamp predicts functional separation in mild familial and severe de novo forms of SCN2A epilepsy. Proc. Natl. Acad. Sci. U. S. A. 115, E5516–E5525.
Not in our library10.1073/pnas.1800077115
22.
Berghuis B. de Kovel C. G. F. van Iterson L. Lamberts R. J. Sander J. W. Lindhout D. (2015 ). Complex SCN8A DNA-abnormalities in an individual with therapy resistant absence epilepsy. Epilepsy Res. 115, 141–144.
Not in our library10.1016/j.eplepsyres.2015.06.007
23.
Berkovic S. F. Heron S. E. Giordano L. Marini C. Guerrini R. Kaplan R. E. (2004 ). Benign Familial Neonatal-Infantile Seizures: Characterization of a New Sodium Channelopathy. Ann. Neurol. 55, 550–557.
Not in our library10.1002/ana.20029
24.
Berkovic S. F. Grinton B. Dixon-Salazar T. Laughlin B. L. Lubbers L. Milder J. (2018 ). De novo variants in the alternative exon 5 of SCN8A cause epileptic encephalopathy. Genet. Med. 20, 275–281.
Not in our library10.1038/gim.2017.100
25.
Bialer M. Johannessen S. I. I. Koepp M. J. Levy R. H. Perucca E. Tomson T. (2018 ). Progress report on new antiepileptic drugs: A summary of the Fourteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIV). I. Drugs preclinical early clinical development. Epilepsia 59, 1811–1841.
Not in our library10.1111/epi.14557
26.
Black J. A. Nikolajsen L. Kroner K. Jensen T. S. Waxman S. G. (2008 ). Multiple sodium channel isoforms and mitogen-activated protein kinases are present in painful human neuromas. Ann. Neurol. 64, 644–653.
Not in our library10.1002/ana.21527
27.
Blanchard M. G. Willemsen M. H. Walker J. B. Dib-Hajj S. D. Waxman S. G. Jongmans M. C. J. (2015 ). De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy. J. Med. Genet. 52, 330–337.
Not in our library10.1136/jmedgenet-2014-102813
28.
Remarkable Phenytoin Sensitivity in 4 Children with SCN8A-related Epilepsy: A Molecular Neuropharmacological Approach · 2016
Corrected
29.
Bouza A. A. Isom L. L. (2018 ). “Voltage-Gated Sodium Channel b Subunits and Their Related Diseases,” in Handbook of experimental pharmacology (Springer International Publishing), 423–450.
Not in our library10.1007/164_2017_48
30.
Braakman H. M. Verhoeven J. S. Erasmus C. E. Haaxma C. A. Willemsen M. H. Schelhaas H. J. (2017 ). Phenytoin as a last-resort treatment in SCN8A encephalopathy. Epilepsia Open 2, 343–344.
Not in our library10.1002/epi4.12059
31.
Brunklaus A. Ellis R. Reavey E. Semsarian C. Zuberi S. M. (2014 ). Genotype phenotype associations across the voltage-gated sodium channel family. J. Med. Genet. 51, 650–658.
Not in our library10.1136/jmedgenet-2014-102608
32.
Brunklaus A. Ellis R. Stewart H. Aylett S. Reavey E. Jefferson R. (2015 ). Homozygous mutations in the SCN1A gene associated with genetic epilepsy with febrile seizures plus and Dravet syndrome in 2 families. Eur. J. Paediatr. Neurol. 19, 484–488.
Not in our library10.1016/j.ejpn.2015.02.001
33.
Buoni S. Orrico A. Galli L. Zannolli R. Burroni L. Hayek J. (2006 ). SCN1 delG) novel truncating mutation with benign outcome of severe myoclonic epilepsy of infancy. Neurology 66, 606–607.
Not in our library10.1212/01.wnl.0000198504.41315.b1
34.
Butler K. M. da Silva C. Alexander J. J. Hegde M. Escayg A. (2017 a). Diagnostic Yield From 339 Epilepsy Patients Screened on a Clinical Gene Panel. Pediatr. Neurol. 77, 61–66.
Not in our library10.1016/j.pediatrneurol.2017.09.003
35.
Butler K. M. da Silva C. Shafir Y. Weisfeld-Adams J. D. Alexander J. J. Hegde M. (2017 b). De novo and inherited SCN8A epilepsy mutations detected by gene panel analysis. Epilepsy Res. 129, 17–25.
Not in our library10.1016/j.eplepsyres.2016.11.002
36.
Caldwell J. H. Schaller K. L. Lasher R. S. Peles E. Levinson S. R. (2000 ). Sodium channel Nav1.6 is localized at nodes of Ranvier, dendrites, and synapses. Proc. Natl. Acad. Sci. 97, 5616–5620.
Not in our library10.1073/pnas.090034797
37.
Capes D. L. Goldschen-Ohm M. P. Arcisio-Miranda M. Bezanilla F. Chanda B. (2013 ). Domain IV voltage-sensor movement is both sufficient and rate limiting for fast inactivation in sodium channels. J. Gen. Physiol. 142, 101–112.
Not in our library10.1085/jgp.201310998
38.
Carranza Rojo D. Hamiwka L. McMahon J. M. Dibbens L. M. Arsov T. Suls A. (2011 ). De novo SCN1A mutations in migrating partial seizures of infancy. Neurology 77, 380–383.
Not in our library10.1212/wnl.0b013e318227046d
39.
Carvill G. L. Heavin S. B. Yendle S. C. McMahon J. M. O’Roak B. J. Cook J. (2013 ). Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1. Nat. Genet. 45, 825–830.
Not in our library10.1038/ng.2646
40.
Catterall W. A. Kalume F. Oakley J. C. (2010 ). NaV1.1 channels and epilepsy. J. Physiol. 588, 1849–1859.
Not in our library10.1113/jphysiol.2010.187484
41.
Catterall W. A. (2014 a). Sodium Channels, Inherited Epilepsy, and Antiepileptic Drugs. Annu. Rev. Pharmacol. Toxicol. 54, 317–338.
Not in our library10.1146/annurevpharmtox-011112-140232
42.
Catterall W. A. (2014 b). Structure and function of voltage-gated sodium channels at atomic resolution. Exp. Physiol. 99, 35–51.
Not in our library10.1113/expphysiol.2013.071969
43.
Catterall W. A. (2017 ). Forty Years of Sodium Channels: Structure, Function, Pharmacology, and Epilepsy. Neurochem. Res. 42, 2495–2504.
Not in our library10.1007/s11064-017-2314-9
44.
Cen Z. Lou Y. Guo Y. Wang J. Feng J. (2017 ). Q10R mutation in SCN9A gene is associated with generalized epilepsy with febrile seizures plus. Seizure 50, 186–188.
Not in our library10.1016/j.seizure.2017.06.023
45.
Cheah C. S. Westenbroek R. E. Roden W. H. Kalume F. Oakley J. C. Jansen L. A. (2013 ). Correlations in timing of sodium channel expression, epilepsy, and sudden death in Dravet syndrome. Channels 7, 468–472.
Not in our library10.4161/chan.26023
46.
Chen Y. H. Dale T. J. Romanos M. A. Whitaker W. R. J. Xie X. M. Clare J. J. (2000 ). Cloning, distribution and functional analysis of the type III sodium channel from human brain. Eur. J. Neurosci. 12, 4281–4289.
Not in our library10.1046/j.1460-9568.2000.01336.x
47.
Cestèle S. Labate A. Rusconi R. Tarantino P. Mumoli L. Franceschetti S. (2013 ). Divergent effects of the T1174S SCN1A mutation associated with seizures and hemiplegic migraine. Epilepsia 54, 927–935.
Not in our library10.1111/epi.12123
48.
Cetica V. Chiari S. Mei D. Parrini E. Grisotto L. Marini C. (2017 ). Clinical and genetic factors predicting Dravet syndrome in infants with SCN1A mutations. Neurology 88, 1037–1044.
Not in our library10.1212/wnl.0000000000003716
49.
Chen Y. J. Shi Y. W. Xu H. Q. Chen M. L. Gao M. M. Sun W. W. (2015 ). Electrophysiological Differences between the Same Pore Region Mutation in SCN1A and SCN3A. Mol. Neurobiol. 51, 1263–1270.
Not in our library10.1007/s12035-014-8802-x
50.
Chong P. F. Saitsu H. Sakai Y. Imagi T. Nakamura R. Matsukura M. (2018 ). Deletions of SCN2A and SCN3A genes in a patient with West syndrome and autistic spectrum disorder. Seizure 60, 91–93.
Not in our library10.1016/j.seizure.2018.06.012
51.
Claes L. Del-Favero J. Ceulemans B. Lagae L. Van Broeckhoven C. De Jonghe P. (2001 ). De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am. J. Hum. Genet. 68, 1327–1332.
Not in our library10.1086/320609
52.
Claes L. Ceulemans B. Audenaert D. Smets K. Löfgren A. Del-Favero J. (2003 ). De novo SCN1A mutations are a major cause of severe myoclonic epilepsy of infancy. Hum. Mutat. 21, 615–621.
Not in our library10.1002/humu.10217
53.
Clairfeuille T. Cloake A. Infield D. T. Llongueras J. P. Arthur C. P. Li Z. R. (2019 ). Structural basis of a-scorpion toxin action on Nav channels. Science 363, 1–25.
Not in our library10.1126/science.aav8573
54.
Meta-analysis of the diagnostic and clinical utility of genome and exome sequencing and chromosomal microarray in children with suspected genetic diseases · 2018
No notice
55.
Colombo E. Franceschetti S. Avanzini G. Mantegazza M. (2013 ). Phenytoin Inhibits the Persistent Sodium Current in Neocortical Neurons by Modifying Its Inactivation Properties. PloS One 8, e55329.
Not in our library10.1371/journal.pone.0055329
56.
Colosimo E. Gambardella A. Mantegazza M. Labate A. Rusconi R. Schiavon E. (2007 ). Electroclinical Features of a Family with Simple Febrile Seizures and Temporal Lobe Epilepsy Associated with SCN1A Loss-of-Function Mutation. Epilepsia 48, 1691–1696.
Not in our library10.1111/j.1528-1167.2007.01153.x
57.
Combi R. Grioni D. Contri M. Redaelli S. Redaelli F. Bassi M. T. (2009 ). Clinical and genetic familial study of a large cohort of Italian children with idiopathic epilepsy. Brain Res. Bull. 79, 89–96.
Not in our library10.1016/j.brainresbull.2009.01.008
58.
Costain G. Cordeiro D. Matviychuk D. Mercimek-Andrews S. (2019 ). Clinical Application of Targeted Next-Generation Sequencing Panels and Whole Exome Sequencing in Childhood Epilepsy. Neuroscience 418, 291–310.
Not in our library10.1016/j.neuroscience.2019.08.016
59.
Cui X. Zeng F. Liu Y. Zhang J. Archacki S. Zhan T. (2011 ). A novel SCN1A missense mutation causes generalized epilepsy with febrile seizures plus in a Chinese family. Neurosci. Lett. 503, 27–30.
Not in our library10.1016/j.neulet.2011.08.001
60.
Cummins T. R. Waxman S. G. (1997 ). Downregulation of tetrodotoxinresistant sodium currents and upregulation of a rapidly repriming tetrodotoxin-sensitive sodium current in small spinal sensory neurons after nerve injury. J. Neurosci. 17, 3503–3514.
Not in our library10.1523/jneurosci.17-10-03503.1997
61.
Cummins T. R. Aglieco F. Renganathan M. Herzog R. I. I. Dib-Hajj S. D. Waxman S. G. (2001 ). Nav1.3 sodium channels: Rapid repriming and slow closed-state inactivation display quantitative differences after expression in a mammalian cell line and in spinal sensory neurons. J. Neurosci. 21, 5952–5961.
Not in our library10.1523/jneurosci.21-16-05952.2001
62.
Daoud H. Luco S. M. Li R. Bareke E. Beaulieu C. Jarinova O. (2016 ). Next-generation sequencing for diagnosis of Rare diseases in the neonatal intensive care unit. Cmaj 188, E254–E260.
Not in our library10.1503/cmaj.150823
63.
Davidsson J. Collin A. Olsson M. E. Lundgren J. Soller M. (2008 ). Deletion of the SCN gene cluster on 2q24.4 is associated with severe epilepsy: An array-based genotype–phenotype correlation and a comprehensive review of previously published cases. Epilepsy Res. 81, 69–79.
Not in our library10.1016/j.eplepsyres.2008.04.018
64.
de Kovel C. G. F. Meisler M. H. Brilstra E. H. van Berkestijn F. M. C. van Lieshout S. (2014 ). Characterization of a de novo SCN8A mutation in a patient with epileptic encephalopathy. Epilepsy Res. 108, 1511–1518.
Not in our library10.1016/j.eplepsyres.2014.08.020
65.
Deciphering Developmental Disorders Study (2015 ). Large-scale discovery of novel genetic causes of developmental disorders. Nature 519, 223–228.
Not in our library10.1038/nature14135
66.
Deng H. Xiu X. Song Z. (2014 ). The molecular biology of genetic-based epilepsies. Mol. Neurobiol. 49, 352–367.
Not in our library10.1007/s12035-013-8523-6
67.
Denis J. Villeneuve N. Cacciagli P. Mignon-Ravix C. Lacoste C. Lefranc J. (2019 ). Clinical study of 19 patients with SCN8A-related epilepsy: Two modes of onset regarding EEG and seizures. Epilepsia 60, 845–856.
Not in our library10.1111/epi.14727
68.
Depienne C. Trouillard O. Saint-Martin C. Gourfinkel-An I. Bouteiller D. Carpentier W. (2008 ). Spectrum of SCN1A gene mutations associated with Dravet syndrome: analysis of 333 patients. J. Med. Genet. 46, 183–191.
Not in our library10.1136/jmg.2008.062323
69.
Devinsky O. Vezzani A. Jette N. De Curtis M. Perucca P. (2018 ). Epilepsy. Nat. Rev. 3, 1–24.
Not in our library10.1038/nrdp.2018.24
70.
Dhamija R. Wirrell E. Falcao G. Kirmani S. Wong-Kisiel L. C. (2013 ). Novel de novo SCN2A Mutation in a Child With Migrating Focal Seizures of Infancy. Pediatr. Neurol. 49, 486–488.
Not in our library10.1016/j.pediatrneurol.2013.07.004
71.
Dhamija R. Erickson M. K. St Louis E. K. Wirrell E. Kotagal S. (2014 ). Sleep Abnormalities in Children With Dravet Syndrome. Pediatr. Neurol. 50, 474–478.
Not in our library10.1016/j.pediatrneurol.2014.01.017
72.
Djémié T. Weckhuysen S. von Spiczak S. Carvill G. L. Jaehn J. Anttonen A.-K. (2016 ). Pitfalls in genetic testing: the story of missed SCN1A mutations. Mol. Genet. Genomic Med. 4, 457–464.
Not in our library10.1002/mgg3.217
73.
Doty C. N. (2010 ). SCN9A: Another sodium channel excited to play a role in human epilepsies. Clin. Genet. 77, 326–328.
Not in our library10.1111/j.1399-0004.2009.01366_1.x
74.
Dyment D. A. Tétreault M. Beaulieu C. L. Hartley T. Ferreira P. Chardon J. W. (2015 ). Whole-exome sequencing broadens the phenotypic spectrum of rare pediatric epilepsy: A retrospective study. Clin. Genet. 88, 34–40.
Not in our library10.1111/cge.12464
75.
Ebach K. Joos H. Doose H. Stephani U. Kurlemann G. Fiedler B. (2005 ). SCN1A mutation analysis in myoclonic astatic epilepsy and severe idiopathic generalized epilepsy of infancy with generalized tonic-clonic seizures. Neuropediatrics 36, 210–213.
Not in our library10.1055/s-2005-865607
76.
Ebrahimi A. Houshmand M. Tonekaboni S. H. Fallah Mahboob Passand M. S. Zainali S. Moghadasi M. (2010 ). Two Novel Mutations in SCN1A Gene in Iranian Patients with Epilepsy. Arch. Med. Res. 41, 207–214.
Not in our library10.1016/j.arcmed.2010.04.007
77.
Egri C. Vilin Y. Y. Ruben P. C. (2012 ). A thermoprotective role of the sodium channel β 1 subunit is lost with the β 1(C121W) mutation. Epilepsia 53, 494–505.
Not in our library10.1111/j.1528-1167.2011.03389.x
78.
Encinas A. C. Moore I. (Ki) M. Watkins J. C. Hammer M. F. (2019 ). Influence of age at seizure onset on the acquisition of neurodevelopmental skills in an SCN8A cohort. Epilepsia 60, 1711–1720.
Not in our library10.1111/epi.16288
79.
Epifanio R. Zanotta N. Giorda R. Bardoni A. Zucca C. (2019 ). Novel epilepsy phenotype associated to a known SCN8A mutation. Seizure 67, 15–17.
Not in our library10.1016/j.seizure.2019.01.017
80.
Escayg A. Heils A. MacDonald B. T. Haug K. Sander T. Meisler M. H. (2001 ). A Novel SCN1A Mutation Associated with Generalized Epilepsy with Febrile Seizures Plus—and Prevalence of Variants in Patients with Epilepsy. Am. J. Hum. Genet. 68, 866–873.
Not in our library10.1086/319524
81.
Escayg A. Goldin A. L. (2010 ). Sodium channel SCN1A and epilepsy: Mutations and mechanisms. Epilepsia 51, 1650–1658.
Not in our library10.1111/j.1528-1167.2010.02640.x
82.
Estacion M. Gasser A. Dib-Hajj S. D. Waxman S. G. (2010 ). A sodium channel mutation linked to epilepsy increases ramp and persistent current of Nav1.3 and induces hyperexcitability in hippocampal neurons. Exp. Neurol. 224, 362–368.
Not in our library10.1016/j.expneurol.2010.04.012
83.
Estacion M. Waxman S. G. (2013 ). The response of NaV1.3 sodium channels to ramp stimuli: Multiple components and mechanisms. J. Neurophysiol. 109, 306–314.
Not in our library10.1152/jn.00438.2012
84.
Estacion M. O’Brien J. E. Conravey A. Hammer M. F. Waxman S. G. Dib-Hajj S. D. (2014 ). A novel de novo mutation of SCN8A (Nav1.6) with enhanced channel activation in a child with epileptic encephalopathy. Neurobiol. Dis. 69, 117–123.
Not in our library10.1016/j.nbd.2014.05.017
85.
Esterhuizen A. II Mefford H. C. Ramesar R. S. Wang S. Carvill G. L. Wilmshurst J. M. (2018 ). Dravet syndrome in South African infants: Tools for an early diagnosis. Seizure 62, 99–105.
Not in our library10.1016/j.seizure.2018.09.010
86.
Falco-Walter J. J. Scheffer I. E. Fisher R. S. (2018 ). The new definition and classification of seizures and epilepsy. Epilepsy Res. 139, 73–79.
Not in our library10.1016/j.eplepsyres.2017.11.015
87.
Felts P. A. Yokoyama S. Dib-Hajj S. Black J. A. Waxman S. G. (1997 ). Sodium channel a-subunit mRNAs I, II, III, NaG, Na6 and hNE (PN1): different expression patterns in developing rat nervous system. Mol. Brain Res. 45, 71–82.
Not in our library10.1016/s0169-328x(96)00241-0
88.
Fisher R. S. Acevedo C. Arzimanoglou A. Bogacz A. Cross J. H. Elger C. E. (2014 ). ILAE Official Report: A practical clinical definition of epilepsy. Epilepsia 55, 475–482.
Not in our library10.1111/epi.12550
89.
Foster L. A. Johnson M. R. MacDonald J. T. Karachunski P. II Henry T. R. Nascene D. R. (2017 ). Infantile Epileptic Encephalopathy Associated With SCN2A Mutation Responsive to Oral Mexiletine. Pediatr. Neurol. 66, 108–111.
Not in our library10.1016/j.pediatrneurol.2016.10.008
90.
Fry A. E. Rees E. Thompson R. Mantripragada K. Blake P. Jones G. (2016 ). Pathogenic copy number variants and SCN1A mutations in patients with intellectual disability and childhood-onset epilepsy. BMC Med. Genet. 17, 34.
Not in our library10.1186/s12881-016-0294-2
91.
Fujiwara T. (2003 ). Mutations of sodium channel alpha subunit type 1 (SCN1A) in intractable childhood epilepsies with frequent generalized tonic-clonic seizures. Brain 126, 531–546.
Not in our library10.1093/brain/awg053
92.
Fukasawa T. Kubota T. Negoro T. Saitoh M. Mizuguchi M. Ihara Y. (2015 ). A case of recurrent encephalopathy with SCN2A missense mutation. Brain Dev. 37, 631–634.
Not in our library10.1016/j.braindev.2014.10.001
93.
Fukuma G. Oguni H. Shirasaka Y. Watanabe K. Miyajima T. Yasumoto S. (2004 ). Mutations of Neuronal Voltage-gated Na+ Channel alpha1 Subunit Gene SCN1A in Core Severe Myoclonic Epilepsy in Infancy (SMEI) and in Borderline SMEI (SMEB). Epilepsia 45, 140–148.
Not in our library10.1111/j.0013-9580.2004.15103.x
94.
Fung L.-W. E. Kwok S.-L. J. Tsui K.-W. S. (2015 ). SCN8A mutations in Chinese children with early onset epilepsy and intellectual disability. Epilepsia 56, 1319–1320.
Not in our library10.1111/epi.12925
95.
Fung C. W. Kwong A. K. Y. Wong V. C. N. (2017 ). Gene panel analysis for nonsyndromic cryptogenic neonatal/infantile epileptic encephalopathy. Epilepsia Open 2, 236–243.
Not in our library10.1002/epi4.12055
96.
Gamal El-Din T. M. Martinez G. Q. Payandeh J. Scheuer T. Catterall W. A. (2013 ). A gating charge interaction required for late slow inactivation of the bacterial sodium channel NavAb. J. Gen. Physiol. 142, 181–190.
Not in our library10.1085/jgp.201311012
97.
Gardella E. Becker F. Møller R. S. Schubert J. Lemke J. R. Larsen L. H. G. (2016 ). Benign infantile seizures and paroxysmal dyskinesia caused by an SCN8A mutation. Ann. Neurol. 79, 428–436.
Not in our library10.1002/ana.24580
98.
Gardella E. Marini C. Trivisano M. Fitzgerald M. P. Alber M. Howell K. B. (2018 ). The phenotype of SCN8A developmental and epileptic encephalopathy. Neurology 91, E1112–E1124.
Not in our library10.1212/wnl.0000000000006199
99.
Gargus J. J. Tournay A. (2007 ). Novel Mutation Confirms Seizure Locus SCN1A is Also Familial Hemiplegic Migraine Locus FHM3. Pediatr. Neurol. 37, 407–410.
Not in our library10.1016/j.pediatrneurol.2007.06.016
100.
Ghovanloo M. R. Aimar K. Ghadiry-Tavi R. Yu A. Ruben P. C. (2016 ). Physiology and Pathophysiology of Sodium Channel Inactivation. Curr. Top. Membr. 78, 479–509.
Not in our library10.1016/bs.ctm.2016.04.001
101.
Gokben S. Onay H. Yilmaz S. Atik T. Serdaroglu G. Tekin H. (2017 ). Targeted next generation sequencing: the diagnostic value in early-onset epileptic encephalopathy. Acta Neurol. Belg. 117, 131–138.
Not in our library10.1007/s13760-016-0709-z
102.
Gilchrist J. Das S. Van Petegem F. Bosmans F. (2013 ). Crystallographic insights into sodium-channel modulation by the b4 subunit. Proc. Natl. Acad. Sci. 110, E5016–E5024.
Not in our library10.1073/pnas.1314557110
103.
Goldin A. L. Escayg A. (2010 ). Sodium channel SCN1A and epilepsy: mutations and mechanisms. Epilepsia 51:16.
Not in our library10.1111/j.1528-1167.2010.02640.x
104.
Goldschen-Ohm M. P. Capes D. L. Oelstrom K. M. Chanda B. (2013 ). Multiple pore conformations driven by asynchronous movements of voltage sensors in a eukaryotic sodium channel. Nat. Commun. 4, 1350.
Not in our library10.1038/ncomms2356
105.
Gorman K. M. King M. D. (2017 ). SCN2A p.Ala263Val Variant a Phenotype of Neonatal Seizures Followed by Paroxysmal Ataxia in Toddlers. Pediatr. Neurol. 67, 111–112.
Not in our library10.1016/j.pediatrneurol.2016.11.008
106.
Grinton B. E. Heron S. E. Pelekanos J. T. Zuberi S. M. Kivity S. Afawi Z. (2015 ). Familial neonatal seizures in 36 families: Clinical and genetic features correlate with outcome. Epilepsia 56, 1071–1080.
Not in our library10.1111/epi.13020
107.
Guerrini R. Cellini E. Mei D. Metitieri T. Petrelli C. Pucatti D. (2010 ). Variable epilepsy phenotypes associated with a familial intragenic deletion of the SCN1A gene. Epilepsia 51, 2474–2477.
Not in our library10.1111/j.1528-1167.2010.02790.x
108.
Hackenberg A. Baumer A. Sticht H. Schmitt B. Kroell-Seger J. Wille D. (2014 ). Infantile Epileptic Encephalopathy, Transient Choreoathetotic Movements, and Hypersomnia due to a De Novo Missense Mutation in the SCN2A Gene. Neuropediatrics 45, 261–264.
Not in our library10.1055/s-0034-1372302
109.
Haginoya K. Togashi N. Kaneta T. Hino-Fukuyo N. Ishitobi M. Kakisaka Y. (2018 ). [18F]fluorodeoxyglucose-positron emission tomography study of genetically confirmed patients with Dravet syndrome. Epilepsy Res. 147, 9–14.
Not in our library10.1016/j.eplepsyres.2018.08.008
110.
Hains B. C. Klein J. P. Saab C. Y. Craner M. J. Black J. A. Waxman S. G. (2003 ). Upregulation of sodium channel Nav1.3 and functional involvement in neuronal hyperexcitability associated with central neuropathic pain after spinal cord injury. J. Neurosci. 23, 8881–8892.
Not in our library10.1523/jneurosci.23-26-08881.2003
111.
Halvorsen M. Petrovski S. Shellhaas R. Tang Y. Crandall L. Goldstein D. (2016 ). Mosaic mutations in early-onset genetic diseases. Genet. Med. 18, 746–749.
Not in our library10.1038/gim.2015.155
112.
Han J. Y. Jang J. H. Lee I. G. Shin S. Park J. (2017 ). A novel inherited mutation of SCN8a in a korean family with benign familial infantile epilepsy using diagnostic exome sequencing. Ann. Clin. Lab. Sci. 47, 747–753.
Not in our library
113.
Han C. Dib-Hajj S. D. Lin Z. Li Y. Eastman E. M. Tyrrell L. (2009 ). Early- and late-onset inherited erythromelalgia: genotypephenotype correlation. Brain 132, 1711–1722.
Not in our library10.1093/brain/awp078
114.
Hammer M. F. Wagnon J. L. Mefford H. C. Meisler M. H. (2016 ). “SCN8A-Related Epilepsy with Encephalopathy,” in GeneReviews® [Internet]. Eds. Adam M. P. Ardinger H. H. Pagon R. A. (Seattle (WA): University of Washington).
Not in our library
115.
Harkin L. A. McMahon J. M. Iona X. Dibbens L. Pelekanos J. T. Zuberi S. M. (2007 ). The spectrum of SCN1A-related infantile epileptic encephalopathies. Brain 130, 843–852.
Not in our library10.1093/brain/awm002
116.
Haug K. Hallmann K. Rebstock J. Dullinger J. Muth S. Haverkamp F. (2001 ). The voltage-gated sodium channel gene SCN2A and idiopathic generalized epilepsy. Epilepsy Res. 47, 243–246.
Not in our library10.1016/s0920-1211(01)00312-6
117.
Haufe V. Camacho J. A. Dumaine R. Günther B. Bollensdorff C. von Banchet G. S. (2005 ). Expression pattern of neuronal and skeletal muscle voltage-gated Na+ channels in the developing mouse heart. J. Physiol. 564, 683–696.
Not in our library10.1113/jphysiol.2004.079681
118.
Herlenius E. Heron S. E. Grinton B. E. Keay D. Scheffer I. E. Mulley J. C. (2007 ). SCN2A mutations and benign familial neonatal-infantile seizures: The phenotypic spectrum. Epilepsia 48, 1138–1142.
Not in our library10.1111/j.1528-1167.2007.01049.x
119.
Hernández Chávez M. Mesa Latorre T. Pedraza Herrera M. Troncoso Schifferli M. (2014 ). ¿Crisis febriles complejas o síndrome de Dravet?: Descripción de 3 casos clínicos. Rev. Chil. pediatría 85, 588–593.
Not in our library10.4067/s0370-41062014000500010
120.
Heron S. E. Crossland K. M. Andermann E. Phillips H. A. Hall A. J. Bleasel A. (2002 ). Sodium-channel defects in benign familial neonatal-infantile seizures. Lancet 360, 851–852.
Not in our library10.1016/s0140-6736(02)09968-3
121.
Heron S. E. Scheffer I. E. Grinton B. E. Eyre H. Oliver K. L. Bain S. (2010 ). Familial neonatal seizures with intellectual disability caused by a microduplication of chromosome 2q24.3. Epilepsia 51, 1865–1869.
Not in our library10.1111/j.1528-1167.2010.02558.x
122.
Hewson S. Brunga L. Ojeda M. F. Imhof E. Patel J. Zak M. (2018 ). Prevalence of Genetic Disorders and GLUT1 Deficiency in a Ketogenic Diet Clinic. Can. J. Neurol. Sci. 45, 93–96.
Not in our library10.1017/cjn.2017.246
123.
Heyne H. O. Artomov M. Battke F. Bianchini C. Smith D. R. Liebmann N. (2019 ). Targeted gene sequencing in 6994 individuals with neurodevelopmental disorder with epilepsy. Genet. Med. 21, 2496–2503.
Not in our library10.1038/s41436-019-0531-0
124.
Hoffman-Zacharska D. Szczepanik E. Terczynska I. Goszczanska-Ciuchta A. Zalewska-Miszkurka Z. Tataj R. (2015 ). From focal epilepsy to dravet syndrome –heterogeneity of the phenotype due to SCN1A mutations of the p.Arg1596 amino acid residue in the nav1.1 subunit. Neurol. Neurochir. Pol. 49, 258–266.
Not in our library10.1016/j.pjnns.2015.06.006
125.
Holland K. D. Kearney J. A. Glauser T. A. Buck G. Keddache M. Blankston J. R. (2008 ). Mutation of sodium channel SCN3A in a patient with cryptogenic pediatric partial epilepsy. Neurosci. Lett. 433, 65–70.
Not in our library10.1016/j.neulet.2007.12.064
126.
Horvath G. A. Demos M. Shyr C. Matthews A. Zhang L. Race S. (2016 ). Secondary neurotransmitter deficiencies in epilepsy caused by voltage-gated sodium channelopathies: A potential treatment target? Mol. Genet. Metab. 117, 42–48.
Not in our library10.1016/j.ymgme.2015.11.008
127.
Howell K. B. McMahon J. M. Carvill G. L. Tambunan D. Mackay M. T. Rodriguez-Casero V. (2015 ). SCN2A encephalopathy. Neurology 85, 958–966.
Not in our library10.1212/wnl.0000000000001926
128.
Hsiao J. Yuan T. Y. Tsai M. S. Lu C. Y. Lin Y. C. Lee M. L. (2016 ). Upregulation of Haploinsufficient Gene Expression in the Brain by Targeting a Long Non-coding RNA Improves Seizure Phenotype in a Model of Dravet Syndrome. EBioMedicine 9, 257–277.
Not in our library10.1016/j.ebiom.2016.05.011
129.
Hu W. Tian C. Li T. Yang M. Hou H. Shu Y. (2009 ). Distinct contributions of Nav1.6 and Nav1.2 in action potential initiation and backpropagation. Nat. Neurosci. 12, 996–1002.
Not in our library10.1038/nn.2359
130.
Structure-based assessment of disease-related mutations in human voltage-gated sodium channels · 2017
No notice
131.
Hussain A. Seinfeld S. Morton L. (2016 ). Genetic association with ictal cardiorespiratory phenomena: SCN8A case series. J. Pediatr. Neurol. 14, 151–155.
Not in our library10.1055/s-0036-1593744
132.
Iannetti P. Parisi P. Spalice A. Ruggieri M. Zara F. (2009 ). Addition of verapamil in the treatment of severe myoclonic epilepsy in infancy. Epilepsy Res. 85, 89–95.
Not in our library10.1016/j.eplepsyres.2009.02.014
133.
Inuzuka L. M. Macedo-Souza L. II Della-Ripa B. Cabral K. S. S. Monteiro F. Kitajima J. P. (2019 ). Neurodevelopmental disorder associated with de novo SCN3A pathogenic variants: two new cases and review of the literature. Brain Dev. 42, 211–216.
Not in our library10.1016/j.braindev.2019.09.004
134.
Israel M. R. Thongyoo P. Deuis J. R. Craik D. J. Vetter I. Durek T. (2018 ). The E15R Point Mutation in Scorpion Toxin Cn2 Uncouples Its Depressant and Excitatory Activities on Human Na V 1.6. J. Med. Chem. 61, 1730–1736.
Not in our library10.1021/acs.jmedchem.7b01609
135.
Ito M. Shirasaka Y. Hirose S. Sugawara T. Yamakawa K. (2004 ). Seizure phenotypes of a family with missense mutations in SCN2A. Pediatr. Neurol. 31, 150–152.
Not in our library10.1016/j.pediatrneurol.2004.02.013
136.
Jain P. Gulati P. Morrison-Levy N. Yau I. Alsowat D. Otsubo H. (2019 ). “Breath holding spells” in a child with SCN8A-related epilepsy: Expanding the clinical spectrum. Seizure 65, 129–130.
Not in our library10.1016/j.seizure.2019.01.020
137.
Diagnostic Yield of Epilepsy Panel Testing in Patients With Seizure Onset Within the First Year of Life · 2019
Not checked
138.
Jiang D. Shi H. Tonggu L. Gamal El-Din T. M. Lenaeus M. J. Zhao Y. (2020 ). Structure of the Cardiac Sodium Channel. Cell 180, 122–134.e10.
Not in our library10.1016/j.cell.2019.11.041
139.
Jingami N. Matsumoto R. Ito H. Ishii A. Ihara Y. Hirose S. (2014 ). A novel SCN1A mutation in a cytoplasmic loop in intractable juvenile myoclonic epilepsy without febrile seizures. Epileptic Disord. 16, 227–231.
Not in our library10.1684/epd.2014.0657
140.
Johannesen K. M. Gardella E. Scheffer I. Howell K. Smith D. M. Helbig I. (2018 ). Early mortality in SCN8A -related epilepsies. Epilepsy Res. 143, 79–81.
Not in our library10.1016/j.eplepsyres.2018.04.008
141.
Johannesen K. M. Gardella E. Encinas A. C. Lehesjoki A. E. Linnankivi T. Petersen M. B. (2019 ). The spectrum of intermediate SCN8A-related epilepsy. Epilepsia 60, 830–844.
Not in our library10.1111/epi.14705
142.
Johnson C. N. Potet F. Thompson M. K. Kroncke B. M. Glazer A. M. Voehler M. W. (2018 ). A Mechanism of Calmodulin Modulation of the Human Cardiac Sodium Channel. Structure 26, 683–694.e3.
Not in our library10.1016/j.str.2018.03.005
143.
Kamiya K. (2004 ). A Nonsense Mutation of the Sodium Channel Gene SCN2A in a Patient with Intractable Epilepsy and Mental Decline. J. Neurosci. 24, 2690–2698.
Not in our library10.1523/jneurosci.3089-03.2004
144.
Kaplan D. I. I. Isom L. L. Petrou S. (2016 ). Role of sodium channels in epilepsy. Cold Spring Harb. Perspect. Med. 6:a022814.
Not in our library10.1101/cshperspect.a022814
145.
Kearney J. Plummer N. Smith M. Kapur J. Cummins T. Waxman S. (2001 ). A gain-of-function mutation in the sodium channel gene Scn2a results in seizures and behavioral abnormalities. Neuroscience 102, 307–317.
Not in our library10.1016/s0306-4522(00)00479-6
146.
Kim Y. O. Bellows S. Mcmahon J. M. Iona X. Damiano J. Dibbens L. (2014 ). Atypical multifocal Dravet syndrome lacks generalized seizures and may show later cognitive decline. Dev. Med. Child Neurol. 56, 85–90.
Not in our library10.1111/dmcn.12322
147.
Kim H. J. Yang D. Kim S. H. Kim B. Kim H. D. Lee J. S. (2019 ). Genetic and clinical features of SCN8A developmental and epileptic encephalopathy. Epilepsy Res. 158, 106222.
Not in our library10.1016/j.eplepsyres.2019.106222
148.
Knupp K. G. Wirrell E. C. (2018 ). Treatment Strategies for Dravet Syndrome. CNS Drugs 32, 335–350.
Not in our library10.1007/s40263-018-0511-y
149.
Kobayashi K. Ohzono H. Shinohara M. Saitoh M. Ohmori I. Ohtsuka Y. (2012 ). Acute encephalopathy with a novel point mutation in the SCN2A gene. Epilepsy Res. 102, 109–112.
Not in our library10.1016/j.eplepsyres.2012.04.016
150.
Kodera H. Kato M. Nord A. S. Walsh T. Lee M. Yamanaka G. (2013 ). Targeted capture and sequencing for detection of mutations causing early onset epileptic encephalopathy. Epilepsia 54, 1262–1269.
Not in our library10.1111/epi.12203
151.
Kothur K. Holman K. Farnsworth E. Ho G. Lorentzos M. Troedson C. (2018 ). Diagnostic yield of targeted massively parallel sequencing in children with epileptic encephalopathy. Seizure 59, 132–140.
Not in our library10.1016/j.seizure.2018.05.005
152.
Kwong A. K. Y. Fung C. W. Chan S. Y. Wong V. C. N. (2012 ). Identification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndrome. PloS One 7, e41802.
Not in our library10.1371/journal.pone.0041802
153.
Laezza F. Lampert A. Kozel M. A. Gerber B. R. Rush A. M. Nerbonne J. M. (2009 ). FGF14 N-terminal splice variants differentially modulate Nav1.2 and Nav1.6-encoded sodium channels. Mol. Cell. Neurosci. 42, 90–101.
Not in our library10.1016/j.mcn.2009.05.007
154.
Lal D. Reinthaler E. M. Dejanovic B. May P. Thiele H. Lehesjoki A.-E. (2016 ). Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes. PloS One 11, e0150426.
Not in our library10.1371/journal.pone.0150426
155.
Lamar T. Vanoye C. G. Calhoun J. Wong J. C. Dutton S. B. Jorge B. S. (2017 ). SCN3A deficiency associated with increased seizure susceptibility. Neurobiol. Dis. 102, 38–48.
Not in our library10.1016/j.nbd.2017.02.006
156.
Larsen J. Carvill G. L. Gardella E. Kluger G. Schmiedel G. Barisic N. (2015 ). The phenotypic spectrum of SCN8A encephalopathy. Neurology 84, 480–489.
Not in our library10.1212/wnl.0000000000001211
157.
Lattanzi S. Brigo F. Trinka E. Zaccara G. Striano P. Del Giovane C. (2020 ). Adjunctive Cannabidiol in Patients with Dravet Syndrome: A Systematic Review and Meta-Analysis of Efficacy and Safety. CNS Drugs 34, 229–241.
Not in our library10.1007/s40263-020-00708-6
158.
Lauxmann S. Boutry-Kryza N. Rivier C. Mueller S. Hedrich U. B. S. Maljevic S. (2013 ). An SCN2A mutation in a family with infantile seizures from Madagascar reveals an increased subthreshold Na+ current. Epilepsia 54, e117–e121.
Not in our library10.1111/epi.12241
159.
Analysis of protein-coding genetic variation in 60,706 humans · 2016
No notice
160.
Le Gal F. Lebon S. Ramelli G. P. Datta A. N. Mercati D. Maier O. (2014 ). When is a child with status epilepticus likely to have Dravet syndrome? Epilepsy Res. 108, 740–747.
Not in our library10.1016/j.eplepsyres.2014.02.019
161.
Lee H.-F. Chi C.-S. Tsai C.-R. Chen C.-H. Wang C.-C. (2014 ). Electroencephalographic features of patients with SCN1A-positive Dravet syndrome. Brain Dev. 37, 599–611.
Not in our library10.1016/j.braindev.2014.10.003
162.
Lemke J. R. 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.
Not in our library10.1111/j.1528-1167.2012.03516.x
163.
Lewis A. H. Raman I. M. (2014 ). Resurgent current of voltage-gated Na+ channels. J. Physiol. 592, 4825–4838.
Not in our library10.1113/jphysiol.2014.277582
164.
Liao W.-P. Shi Y.-W. Long Y.-S. Zeng Y. Li T. Yu M.-J. (2010 a). Partial epilepsy with antecedent febrile seizures and seizure aggravation by antiepileptic drugs: Associated with loss of function of Nav1.1. Epilepsia 51, 1669–1678.
Not in our library10.1111/j.1528-1167.2010.02645.x
165.
Liao Y. Deprez L. Maljevic S. Pitsch J. Claes L. Hristova D. (2010 b). Molecular correlates of age-dependent seizures in an inherited neonatal-infantile epilepsy. Brain 133, 1403–1414.
Not in our library10.1093/brain/awq057
166.
Lim B. C. Hwang H. Chae J. H. Choi J.-E. Hwang Y. S. Kang S.-H. (2011 ). SCN1A mutational analysis in Korean patients with Dravet syndrome. Seizure 20, 789–794.
Not in our library10.1016/j.seizure.2011.08.002
167.
Lin K. M. Su G. Wang F. Zhang X. Wang Y. Ren J. (2019 ). A de novo SCN8A heterozygous mutation in a child with epileptic encephalopathy: A case report. BMC Pediatr. 19, 400.
Not in our library10.1186/s12887-019-1796-9
168.
Lindy A. S. Stosser M. B. Butler E. Downtain-Pickersgill C. Shanmugham A. Retterer K. (2018 ). Diagnostic outcomes for genetic testing of 70 genes in 8565 patients with epilepsy and neurodevelopmental disorders. Epilepsia 59, 1062–1071.
Not in our library10.1111/epi.14074
169.
Liu J. Tong L. Song S. Niu Y. Li J. Wu X. (2018 ). Novel and de novo mutations in pediatric refractory epilepsy. Mol. Brain 11, 48.
Not in our library10.1186/s13041-018-0392-5
170.
Liu Y. Schubert J. Sonnenberg L. Helbig K. L. Hoei-Hansen C. E. Koko M. (2019 ). Neuronal mechanisms of mutations in SCN8A causing epilepsy or intellectual disability. Brain 142, 376–390.
Not in our library10.1093/brain/awy326
171.
Lossin C. Rhodes T. H. Desai R. R. Vanoye C. G. Wang D. Carniciu S. (2003 ). Epilepsy-Associated Dysfunction in the Voltage-Gated Neuronal Sodium Channel SCN1A. J. Neurosci. 23, 11289–11295.
Not in our library10.1523/jneurosci.23-36-11289.2003
172.
Lossin C. Shi X. Rogawski M. A. Hirose S. (2012 ). Compromised function in the Nav1.2 Dravet syndrome mutation R1312T. Neurobiol. Dis. 47, 378–384.
Not in our library10.1016/j.nbd.2012.05.017
173.
Lucas P. T. Meadows L. S. Nicholls J. Ragsdale D. S. (2005 ). An epilepsy mutation in the β1 subunit of the voltage-gated sodium channel results in reduced channel sensitivity to phenytoin. Epilepsy Res. 64, 77–84.
Not in our library10.1016/j.eplepsyres.2005.03.003
174.
Maier S. K. G. Westenbroek R. E. Schenkman K. A. Feigl E. O. Scheuer T. Catterall W. A. (2002 ). An unexpected role for brain-type sodium channels in coupling of cell surface depolarization to contraction in the heart. Proc. Natl. Acad. Sci. U. S. A. 99, 4073–4078.
Not in our library10.1073/pnas.261705699
175.
Mak C. M. Chan K. Y. W. Yau E. K. C. Chen S. P. L. Siu W. K. Law C. Y. (2011 ). Genetic diagnosis of severe myoclonic epilepsy of infancy (Dravet syndrome) with SCN1A mutations in the Hong Kong Chinese patients. Hong Kong Med. J. = Xianggang yi xue za zhi 17, 500–502.
Not in our library
176.
Makinson C. D. Tanaka B. S. Sorokin J. M. Wong J. C. Christian C. A. Goldin A. L. (2017 ). Regulation of Thalamic and Cortical Network Synchrony by Scn8a. Neuron 93, 1165–1179.e6.
Not in our library10.1016/j.neuron.2017.01.031
177.
Malcolmson J. Kleyner R. Tegay D. Adams W. Ward K. Coppinger J. (2016 ). SCN8A mutation in a child presenting with seizures and developmental delays. Cold Spring Harb. Mol. Case Stud. 2, a001073.
Not in our library10.1101/mcs.a001073
178.
Malo D. Schurr E. Dorfman J. Canfield V. Levenson R. Gros P. (1991 ). Three brain sodium channel a-subunit genes are clustered on the proximal segment of mouse chromosome 2. Genomics 10, 666–672.
Not in our library10.1016/0888-7543(91)90450-s
179.
Malo M. S. Blanchard B. J. Andresen J. M. Srivastava K. Chen X.-N. Li X. (1994 ). Localization of a putative human brain sodium channel gene (SCN1A) to chromosome band 2q24. Cytogenet. Genome Res. 67, 178–186.
Not in our library10.1159/000133818
180.
Mantegazza M. Gambardella A. Rusconi R. Schiavon E. Annesi F. Cassulini R. R. (2005 ). Identification of an Nav1.1 sodium channel (SCN1A) loss-of-function mutation associated with familial simple febrile seizures. Proc. Natl. Acad. Sci. U. S. A. 102, 18177–18182.
Not in our library10.1073/pnas.0506818102
181.
Marini C. Mei D. Temudo T. Ferrari A. R. Buti D. Dravet C. (2007 ). Idiopathic Epilepsies with Seizures Precipitated by Fever and SCN1A Abnormalities. Epilepsia 48, 1678–1685.
Not in our library10.1111/j.1528-1167.2007.01122.x
182.
Clinical whole-genome sequencing in severe early-onset epilepsy reveals new genes and improves molecular diagnosis · 2014
No notice
183.
Mason E. R. Wu F. Patel R. R. Xiao Y. Cannon S. C. Cummins T. R. (2019 ). Resurgent and gating pore currents induced by De Novo SCN2A epilepsy mutations. eNeuro 6, 1–17, ENEURO.0141–19.2019.
Not in our library10.1523/eneuro.0141-19.2019
184.
Mason E. R. Cummins T. R. (2020 ). Differential inhibition of human Nav1.2 resurgent and persistent sodium currents by cannabidiol and GS967. Int. J. Mol. Sci. 21, 1–21.
Not in our library10.3390/ijms21072454
185.
Matalon D. Goldberg E. Medne L. Marsh E. D. (2014 ). Confirming an expanded spectrum of SCN2A mutations: a case series. Epileptic Disord. 16, 13–18.
Not in our library10.1684/epd.2014.0641
186.
McMichael G. Bainbridge M. N. Haan E. Corbett M. Gardner A. Thompson S. (2015 ). Whole-exome sequencing points to considerable genetic heterogeneity of cerebral palsy. Mol. Psychiatry 20, 176–182.
Not in our library10.1038/mp.2014.189
187.
McNally M. A. Johnson J. Huisman T. A. Poretti A. Baranano K. W. Baschat A. A. (2016 ). SCN8A Epileptic Encephalopathy: Detection of Fetal Seizures Guides Multidisciplinary Approach to Diagnosis and Treatment. Pediatr. Neurol. 64, 87–91.
Not in our library10.1016/j.pediatrneurol.2016.08.003
188.
Mei D. Parrini E. Marini C. Guerrini R. (2017 ). The Impact of Next- Generation Sequencing on the Diagnosis and Treatment of Epilepsy in Paediatric Patients. Mol. Diagnosis Ther. 21, 357–373.
Not in our library10.1007/s40291-017-0257-0
189.
Meisler M. H. O’Brien J. E. Sharkey L. M. (2010 ). Sodium channel gene family: Epilepsy mutations, gene interactions and modifier effects. J. Physiol. 588, 1841–1848.
Not in our library10.1113/jphysiol.2010.188482
190.
Meng H. Xu H. Q. Yu L. Lin G. W. He N. Su T. (2015 ). The SCN1A Mutation Database: Updating Information and Analysis of the Relationships among Genotype, Functional Alteration, and Phenotype. Hum. Mutat. 36, 573–580.
Not in our library10.1002/humu.22782
191.
Mercimek-Mahmutoglu S. Patel J. Cordeiro D. Hewson S. Callen D. Donner E. J. (2015 ). Diagnostic yield of genetic testing in epileptic encephalopathy in childhood. Epilepsia 56, 707–716.
Not in our library10.1111/epi.12954
192.
Misra S. N. Kahlig K. M. George A. L. (2008 ). Impaired Na V 1.2 function and reduced cell surface expression in benign familial neonatal-infantile seizures. Epilepsia 49, 1535–1545.
Not in our library10.1111/j.1528-1167.2008.01619.x
193.
Miyatake S. Kato M. Sawaishi Y. Saito T. Nakashima M. Mizuguchi T. (2018 ). Recurrent SCN3A p.Ile875Thr variant in patients with polymicrogyria. Ann. Neurol. 84, 159–161.
Not in our library10.1002/ana.25256
194.
Møller R. S. Larsen L. H. G. Johannesen K. M. Talvik I. Talvik T. Vaher U. (2016 ). Gene panel testing in epileptic encephalopathies and familial epilepsies. Mol. Syndromol. 7, 210–219.
Not in our library10.1159/000448369
195.
Morano A. Fanella M. Albini M. Cifelli P. Palma E. Giallonardo A. T. (2020 ). Cannabinoids in the treatment of epilepsy: Current status and future prospects. Neuropsychiatr. Dis. Treat. 16, 381–396.
Not in our library10.2147/ndt.s203782
196.
Morimoto M. Mazaki E. Nishimura A. Chiyonobu T. Sawai Y. Murakami A. (2006 ). SCN1A Mutation Mosaicism in a Family with Severe Myoclonic Epilepsy in Infancy. Epilepsia 47, 1732–1736.
Not in our library10.1111/j.1528-1167.2006.00645.x
197.
Mulley J. C. Hodgson B. McMahon J. M. Iona X. Bellows S. Mullen S. A. (2013 ). Role of the sodium channel SCN9A in genetic epilepsy with febrile seizures plus and Dravet syndrome. Epilepsia 54, e122–e126.
Not in our library10.1111/epi.12323
198.
Musto E. Gardella E. Møller R. S. (2020 ). Recent advances in treatment of epilepsy-related sodium channelopathies. Eur. J. Paediatr. Neurol. 24, 123–128.
Not in our library10.1016/j.ejpn.2019.12.009
199.
Myers K. A. Burgess R. Afawi Z. Damiano J. A. Berkovic S. F. Hildebrand M. S. (2017 a). De novo SCN1A pathogenic variants in the GEFS+ spectrum: Not always a familial syndrome. Epilepsia 58, e26–e30.
Not in our library10.1111/epi.13649
200.
Myers K. A. McMahon J. M. Mandelstam S. A. Mackay M. T. Kalnins R. M. Leventer R. J. (2017 b). Fatal Cerebral Edema With Status Epilepticus in Children With Dravet Syndrome: Report of 5 Cases. Pediatrics 139, e20161933.
Not in our library10.1542/peds.2016-1933
201.
Nabbout R. Gennaro E. Dalla Bernardina B. Dulac O. Madia F. Bertini E. (2003 ). Spectrum of SCN1A mutations in severe myoclonic epilepsy of infancy. Neurology 60, 1961–1967.
Not in our library10.1212/01.wnl.0000069463.41870.2f
202.
Nabbout R. Copioli C. Chipaux M. Chemaly N. Desguerre I. Dulac O. (2011 ). Ketogenic diet also benefits Dravet syndrome patients receiving stiripentol: A prospective pilot study. Epilepsia 52, 54–57.
Not in our library10.1111/j.1528-1167.2011.03107.x
203.
Nakamura K. Kato M. Osaka H. Yamashita S. Nakagawa E. Haginoya K. (2013 ). Clinical spectrum of SCN2A mutations expanding to Ohtahara syndrome. Neurology 81, 992–998.
Not in our library10.1212/wnl.0b013e3182a43e57
204.
Need A. C. Shashi V. Hitomi Y. Schoch K. Shianna K. V. McDonald M. T. (2012 ). Clinical application of exome sequencing in undiagnosed genetic conditions. J. Med. Genet. 49, 353–361.
Not in our library10.1136/jmedgenet-2012-100819
205.
Ng S. B. Buckingham K. J. Lee C. Bigham A. W. Tabor H. K. Dent K. M. (2010 ). Exome sequencing identifies the cause of a mendelian disorder. Nat. Genet. 42, 30–35.
Not in our library10.1038/ng.499
206.
Nguyen H. M. Goldin A. L. (2010 ). Sodium channel carboxyl-terminal residue regulates fast inactivation. J. Biol. Chem. 285, 9077–9089.
Not in our library10.1074/jbc.m109.054940
207.
Nicita F. Spalice A. Papetti L. Ursitti F. Parisi P. Gennaro E. (2010 ). Genotype-phenotype correlations in a group of 15 SCN1A-mutated italian patients with GEFS+ spectrum (seizures plus, classical and borderline severe myoclonic epilepsy of infancy). J. Child Neurol. 25, 1369–1376.
Not in our library10.1177/0883073810365737
208.
Nishri D. Blumkin L. Lev D. Leshinsky-Silver E. Abu-Rashid M. Birch R. (2010 ). Hepatic coma culminating in severe brain damage in a child with a SCN1A mutation. Eur. J. Paediatr. Neurol. 14, 456–459.
Not in our library10.1016/j.ejpn.2010.03.002
209.
Noujaim S. F. Kaur K. Milstein M. Jones J. M. Furspan P. Jiang D. (2012 ). A null mutation of the neuronal sodium channel Na V 1.6 disrupts action potential propagation and excitation-contraction coupling in the mouse heart. FASEB J. 26, 63–72.
Not in our library10.1096/fj.10-179770
210.
Oates S. Tang S. Rosch R. Lear R. Hughes E. F. Williams R. E. (2018 ). Incorporating epilepsy genetics into clinical practice: A 360°evaluation. NPJ Genomic Med. 3, 13.
Not in our library10.1038/s41525-018-0052-9
211.
O’Brien J. E. Sharkey L. M. Vallianatos C. N. Han C. Blossom J. C. Yu T. (2012 ). Interaction of Voltage-gated Sodium Channel Na v 1.6 ( SCN8A ) with Microtubule-associated Protein Map1b. J. Biol. Chem. 287, 18459–18466.
Not in our library10.1074/jbc.m111.336024
212.
Oelstrom K. Goldschen-ohm M. P. Holmgren M. Chanda B. (2014 ). Evolutionarily conserved intracellular gate of voltage-dependent sodium channels. Nat. Commun. 5, 1–9.
Not in our library10.1038/ncomms4420
213.
Ogiwara I. Ito K. Sawaishi Y. Osaka H. Mazaki E. Inoue I. (2009 ). De novo mutations of voltage-gated sodium channel αiI gene SCN2A in intractable epilepsies. Neurology 73, 1046–1053.
Not in our library10.1212/wnl.0b013e3181b9cebc
214.
Ohashi T. Akasaka N. Kobayashi Y. Magara S. Kawashima H. Matsumoto N. (2014 ). Infantile epileptic encephalopathy with a hyperkinetic movement disorder and hand stereotypies associated with a novel SCN1A mutation. Epileptic Disord. 16, 208–212.
Not in our library10.1684/epd.2014.0649
215.
Ohba C. Kato M. Takahashi S. Lerman-Sagie T. Lev D. Terashima H. (2014 ). Early onset epileptic encephalopathy caused by de novo SCN8A mutations. Epilepsia 55, 994–1000.
Not in our library10.1111/epi.12668
216.
Ohmori I. Kahlig K. M. Rhodes T. H. Wang D. W. George A. L. (2006 ). Nonfunctional SCN1A Is Common in Severe Myoclonic Epilepsy of Infancy. Epilepsia 47, 1636–1642.
Not in our library10.1111/j.1528-1167.2006.00643.x
217.
Oliva M. Berkovic S. F. Petrou S. (2012 ). Sodium channels and the neurobiology of epilepsy. Epilepsia 53, 1849–1859.
Not in our library10.1111/j.1528-1167.2012.03631.x
218.
Oliva M. K. Mcgarr T. C. Beyer B. J. Gazina E. Kaplan D. II Cordeiro L. (2014 ). Physiological and genetic analysis of multiple sodium channel variants in a model of genetic absence epilepsy. Neurobiol. Dis. 67, 180–190.
Not in our library10.1016/j.nbd.2014.03.007
219.
Olson H. E. Tambunan D. LaCoursiere C. Goldenberg M. Pinsky R. Martin E. (2015 ). Mutations in epilepsy and intellectual disability genes in patients with features of Rett syndrome. Am. J. Med. Genet. Part A 167, 2017–2025.
Not in our library10.1002/ajmg.a.37132
220.
Orrico A. Galli L. Grosso S. Buoni S. Pianigiani R. Balestri P. (2009 ). Mutational analysis of the SCN1A, SCN1B and GABRG2 genes in 150 Italian patients with idiopathic childhood epilepsies. Clin. Genet. 75, 579–581.
Not in our library10.1111/j.1399-0004.2009.01155.x
221.
Orsini A. Zara F. Striano P. (2018 ). Recent advances in epilepsy genetics. Neurosci. Lett. 667, 4–9.
Not in our library10.1016/j.neulet.2017.05.014
222.
Ortiz Madinaveitia S. Serrano Madrid M. L. Conejo Moreno D. Sagarra Mur D. Jiménez Corral C. Gutiérrez Álvarez Á.M. (2017 ). Encefalopatía epiléptica de inicio precoz en un paciente con mutación en SCN8A. Rev. Neurol. 65, 572.
Not in our library10.33588/rn.6512.2017426
223.
Pan Y. Cummins T. R. (2020 ). Distinct functional alterations in SCN8A epilepsy mutant channels. J. Physiol. 598, 381–401.
Not in our library10.1113/jp278952
224.
Parrini E. Marini C. Mei D. Galuppi A. Cellini E. Pucatti D. (2017 ). Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes. Hum. Mutat. 38, 216–225.
Not in our library10.1002/humu.23149
225.
Patel R. R. Barbosa C. Brustovetsky T. Brustovetsky N. Cummins T. R. (2016 ). Aberrant epilepsy-associated mutant Nav1.6 sodium channel activity can be targeted with cannabidiol. Brain 139, 2164–2181.
Not in our library10.1093/brain/aww129
226.
Payandeh J. Gamal El-Din T. M. Scheuer T. Zheng N. Catterall W. A. (2012 ). Crystal structure of a voltage-gated sodium channel in two potentially inactivated states. Nature 486, 135–139.
Not in our library10.1038/nature11077
227.
Perucca P. Perucca E. (2019 ). Identifying mutations in epilepsy genes:Impact on treatment selection. Epilepsy Res. 152, 18–30.
Not in our library10.1016/j.eplepsyres.2019.03.001
228.
Pescucci C. Caselli R. Grosso S. Mencarelli M. A. Mari F. Farnetani M. A. (2007 ). 2q24–q31 Deletion: Report of a case and review of the literature. Eur. J. Med. Genet. 50, 21–32.
Not in our library10.1016/j.ejmg.2006.09.001
229.
Peters C. H. Sokolov S. Rajamani S. Ruben P. C. (2013 ). Effects of the antianginal drug, ranolazine, on the brain sodium channel NaV1.2 and its modulation by extracellular protons. Br. J. Pharmacol. 169, 704–716.
Not in our library10.1111/bph.12150
230.
Petrelli C. Passamonti C. Cesaroni E. Mei D. Guerrini R. Zamponi N. (2012 ). Early clinical features in Dravet syndrome patients with and without SCN1A mutations. Epilepsy Res. 99, 21–27.
Not in our library10.1016/j.eplepsyres.2011.10.010
231.
Pons L. Lesca G. Sanlaville D. Chatron N. Labalme A. Manel V. (2018 ). Neonatal tremor episodes and hyperekplexia-like presentation at onset in a child with SCN8A developmental and epileptic encephalopathy. Epileptic Disord. 20, 289–294.
Not in our library10.1684/epd.2018.0988
232.
Genic Intolerance to Functional Variation and the Interpretation of Personal Genomes · 2013
Corrected
233.
Plummer N. W. McBurney M. W. Meisler M. H. (1997 ). Alternative Splicing of the Sodium Channel SCN8A Predicts a Truncated Two-domain Protein in Fetal Brain and Non-neuronal Cells. J. Biol. Chem. 272, 24008–24015.
Not in our library10.1074/jbc.272.38.24008
234.
Poryo M. Clasen O. Oehl-Jaschkowitz B. Christmann A. Gortner L. Meyer S. (2017 ). Dravet syndrome: a new causative SCN1A mutation? Clin. Case Rep. 5, 613–615.
Not in our library10.1002/ccr3.787
235.
Ranza E. Z’Graggen W. Lidgren M. Beghetti M. Guipponi M. Antonarakis S. E. (2020 ). SCN8A heterozygous variants are associated with anoxic-epileptic seizures. Am. J. Med. Genet. Part A..
Not in our library10.1002/ajmg.a.61513
236.
Rauch A. Wieczorek D. Graf E. Wieland T. Endele S. Schwarzmayr T. (2012 ). Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study. Lancet 380, 1674–1682.
Not in our library10.1016/s0140-6736(12)61480-9
237.
Raymond G. Wohler E. Dinsmore C. Cox J. Johnston M. Batista D. (2011 ). An interstitial duplication at 2q24.3 involving the SCN1A, SCN2A, SCN3A genes associated with infantile epilepsy. Am. J. Med. Genet. Part A 155, 920–923.
Not in our library10.1002/ajmg.a.33929
238.
Reif P. S. Tsai M. H. Helbig I. Rosenow F. Klein K. M. (2017 ). Precision medicine in genetic epilepsies: break of dawn? Expert Rev. Neurother. 17, 381–392.
Not in our library10.1080/14737175.2017.1253476
239.
Reyes I. S. Hsieh D. T. Laux L. C. Wilfong A. A. (2011 ). Alleged Cases of Vaccine Encephalopathy Rediagnosed Years Later as Dravet Syndrome. Pediatrics 128.
Not in our library10.1542/peds.2010-0887
240.
Reynolds C. King M. D. Gorman K. M. (2020 ). The phenotypic spectrum of SCN2A-related epilepsy. Eur. J. Paediatr. Neurol. 24, 117–122.
Not in our library10.1016/j.ejpn.2019.12.016
241.
Rhodes T. H. Vanoye C. G. Ohmori I. Ogiwara I. Yamakawa K. George A. L. (2005 ). Sodium channel dysfunction in intractable childhood epilepsy with generalized tonic-clonic seizures. J. Physiol. 569, 433–445.
Not in our library10.1113/jphysiol.2005.094326
242.
Riban V. Fitzsimons H. L. During M. J. (2009 ). Gene therapy in epilepsy. Epilepsia 50, 24–32.
Not in our library10.1111/j.1528-1167.2008.01743.x
243.
Richards K. L. Milligan C. J. Richardson R. J. Jancovski N. Grunnet M. Jacobson L. H. (2018 ). Selective NaV1.1 activation rescues Dravet syndrome mice from seizures and premature death. Proc. Natl. Acad. Sci. U.S. A. 115, E8077–E8085.
Not in our library10.1073/pnas.1804764115
244.
Rilstone J. J. Coelho F. M. Minassian B. A. Andrade D. M. (2012 ). Dravet syndrome: Seizure control and gait in adults with different SCN1A mutations. Epilepsia 53, 1421–1428.
Not in our library10.1111/j.1528-1167.2012.03583.x
245.
Rim J. H. Kim S. H. Hwang I. S. Kwon S. S. Kim J. Kim H. W. (2018 ). Efficient strategy for the molecular diagnosis of intractable early-onset epilepsy using targeted gene sequencing. BMC Med. Genomics 11, 6.
Not in our library10.1186/s12920-018-0320-7
246.
Riva D. Vago C. Pantaleoni C. Bulgheroni S. Mantegazza M. Franceschetti S. (2009 ). Progressive neurocognitive decline in two children with Dravet syndrome, de novo SCN1A truncations and different epileptic phenotypes. Am. J. Med. Genet. Part A 149A, 2339–2345.
Not in our library10.1002/ajmg.a.33029
247.
Rolvien T. Butscheidt S. Jeschke A. Neu A. Denecke J. Kubisch C. (2017 ). Severe bone loss and multiple fractures in SCN8A-related epileptic encephalopathy. Bone 103, 136–143.
Not in our library10.1016/j.bone.2017.06.025
248.
Rossi M. El-Khechen D. Black M. H. Farwell Hagman K. D. Tang S. Powis Z. (2017 ). Outcomes of Diagnostic Exome Sequencing in Patients With Diagnosed or Suspected Autism Spectrum Disorders. Pediatr. Neurol. 70, 34–43.e2.
Not in our library10.1016/j.pediatrneurol.2017.01.033
249.
Rubinstein M. Westenbroek R. E. Yu F. H. Jones C. J. Scheuer T. Catterall W. A. (2015 ). Genetic background modulates impaired excitability of inhibitory neurons in a mouse model of Dravet syndrome. Neurobiol. Dis. 73, 106–117.
Not in our library10.1016/j.nbd.2014.09.017
250.
Rush A. M. Dib-Hajj S. D. Liu S. Cummins T. R. Black J. A. Waxman S. G. (2018 ). “A Single Sodium Channel Mutation Produces Hyperor Hypoexcitability In Different Types Of Neurons,” in Chasing Men on Fire (PNAS: The MIT Press), 89–101.
Not in our library10.7551/mitpress/10310.003.0014
251.
Saitoh M. Shinohara M. Hoshino H. Kubota M. Amemiya K. Takanashi J. (2012 ). Mutations of the SCN1A gene in acute encephalopathy. Epilepsia 53, 558–564.
Not in our library10.1111/j.1528-1167.2011.03402.x
252.
Saitoh M. Ishii A. Ihara Y. Hoshino A. Terashima H. Kubota M. (2015 a). Missense mutations in sodium channel SCN1A and SCN2A predispose children to encephalopathy with severe febrile seizures. Epilepsy Res. 117, 1–6.
Not in our library10.1016/j.eplepsyres.2015.08.001
253.
Saitoh M. Shinohara M. Ishii A. Ihara Y. Hirose S. Shiomi M. (2015 b). Clinical and genetic features of acute encephalopathy in children taking theophylline. Brain Dev. 37, 463–470.
Not in our library10.1016/j.braindev.2014.07.010
254.
Samanta D. Ramakrishnaiah R. (2015 ). De novo R853Q mutation of SCN2A gene and West syndrome. Acta Neurol. Belg. 115, 773–776.
Not in our library10.1007/s13760-015-0454-8
255.
Sanders S. J. Campbell A. J. Cottrell J. R. Moller R. S. Wagner F. F. Auldridge A. L. (2018 ). Progress in Understanding and Treating SCN2A –Mediated Disorders. Trends Neurosci. 41, 442–456.
Not in our library10.1016/j.tins.2018.03.011
256.
Sands T. T. Choi H. (2017 ). Genetic Testing in Pediatric Epilepsy. Curr. Neurol. Neurosci. Rep. 17, 1–11.
Not in our library10.1007/s11910-017-0753-y
257.
Saxena S. Li S. (2017 ). Defeating epilepsy: A global public health commitment. Epilepsia Open 2, 153–155.
Not in our library10.1002/epi4.12010
258.
Scalmani P. Rusconi R. Armatura E. Zara F. Avanzini G. Franceschetti S. (2006 ). Effects in neocortical neurons of mutations of the Nav1.2 Na+ channel causing benign familial neonatal-infantile seizures. J. Neurosci. 26, 10100–10109.
Not in our library10.1523/jneurosci.2476-06.2006
259.
Schreiber J. M. Tochen L. Brown M. Evans S. Ball L. J. Bumbut A. (2020 ). A multi-disciplinary clinic for SCN8A-related epilepsy. Epilepsy Res. 159, 106261.
Not in our library10.1016/j.eplepsyres.2019.106261
260.
Schwarz N. Hahn A. Bast T. Müller S. Löffler H. Maljevic S. (2016 ). Mutations in the sodium channel gene SCN2A cause neonatal epilepsy with late-onset episodic ataxia. J. Neurol. 263, 334–343.
Not in our library10.1007/s00415-015-7984-0
261.
Schiavon E. Sacco T. Cassulini R. R. Gurrola G. Tempia F. Possani L. D. (2006 ). Resurgent Current and Voltage Sensor Trapping Enhanced Activation by a b-Scorpion Toxin Solely in Na v 1.6 Channel. J. Biol. Chem. 281, 20326–20337.
Not in our library10.1074/jbc.m600565200
262.
Sharkey L. M. Jones J. M. Hedera P. Meisler M. H. (2009 ). Evaluation of SCN8A as a candidate gene for autosomal dominant essential tremor. Park. Relat. Disord. 15, 321–323.
Not in our library10.1016/j.parkreldis.2008.06.010
263.
Sheets P. L. Heers C. Stoehr T. Cummins T. R. (2008 ). Differential block of sensory neuronal voltage-gated sodium channels by lacosamide [(2R)-2- (acetylamino)-N-benzyl-3-methoxypropanamide], lidocaine, and carbamazepine. J. Pharmacol. Exp. Ther. 326, 89–99.
Not in our library10.1124/jpet.107.133413
264.
Shen H. Zhou Q. Pan X. Li Z. Wu J. Yan N. (2017 ). Structure of a eukaryotic voltage-gated sodium channel at near-atomic resolution. Science 355, 1–12.
Not in our library10.1126/science.aal4326
265.
Shi X. Yasumoto S. Nakagawa E. Fukasawa T. Uchiya S. Hirose S. (2009 ). Missense mutation of the sodium channel gene SCN2A causes Dravet syndrome. Brain Dev. 31, 758–762.
Not in our library10.1016/j.braindev.2009.08.009
266.
Shi X. Y. Tomonoh Y. Wang W. Z. Ishii A. Higurashi N. Kurahashi H. (2016 ). Efficacy of antiepileptic drugs for the treatment of Dravet syndrome with different genotypes. Brain Dev. 38, 40–46.
Not in our library10.1016/j.braindev.2015.06.008
267.
Silva J. R. Goldstein S. A. N. (2013 ). Voltage-sensor movements describe slow inactivation of voltage-gated sodium channels I: Wild-type skeletal muscle NAv1.4. J. Gen. Physiol. 141, 309–321. 10.1085/jgp.201210909
Not in our library10.1085/jgp.201210909
268.
A Role of SCN9A in Human Epilepsies, As a Cause of Febrile Seizures and As a Potential Modifier of Dravet Syndrome · 2009
No notice
269.
Singh R. Jayapal S. Goyal S. Jungbluth H. Lascelles K. (2015 ). Early-onset movement disorder and epileptic encephalopathy due to de novo dominant SCN8A mutation. Seizure 26, 69–71.
Not in our library10.1016/j.seizure.2015.01.017
270.
Skjei K. L. Church E. W. Harding B. N. Santi M. Holland-Bouley K. D. Clancy R. R. (2015 ). Clinical and histopathological outcomes in patients with SCN1A mutations undergoing surgery for epilepsy. J. Neurosurg. Pediatr. 16, 668–674.
Not in our library10.3171/2015.5.peds14551
271.
Smith R. S. Kenny C. J. Ganesh V. Jang A. Borges-Monroy R. Partlow J. N. (2018 ). Sodium Channel SCN3A (NaV1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development. Neuron 99, 905–913.e7.
Not in our library10.1016/j.neuron.2018.07.052
272.
Spampanato J. (2004 ). A Novel Epilepsy Mutation in the Sodium Channel SCN1A Identifies a Cytoplasmic Domain for Subunit Interaction. J. Neurosci. 24, 10022–10034.
Not in our library10.1523/jneurosci.2034-04.2004
273.
Sone D. Sugawara T. Sakakibara E. Tomioka Y. Taniguchi G. Murata Y. (2012 ). A case of autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) coexisting with pervasive developmental disorder harboring SCN1A mutation in addition to CHRNB2 mutation. Epilepsy Behav. 25, 192–195.
Not in our library10.1016/j.yebeh.2012.07.027
274.
Stoke Therapeutics (2018 ). Stoke Therapeutics Presents Data Showing Single Dose of ASO Therapy Restores Normal Protein Levels in Animal Model of Genetic Epilepsy. Available at: https://www.stoketherapeutics.com/press-releases/stoketherapeutics-presents-data-showing-single-dose-of-aso-therapy-restoresnormal-protein-levels-in-animal-model-of-genetic-epilepsy/ (Accessed December 2, 2020).
Not in our library
275.
Sprissler R. S. Wagnon J. L. Bunton-Stasyshyn R. K. Meisler M. H. Hammer M. F. (2017 ). Altered gene expression profile in a mouse model of SCN8A encephalopathy. Exp. Neurol. 288, 134–141.
Not in our library10.1016/j.expneurol.2016.11.002
276.
Striano P. Bordo L. Lispi M. L. Specchio N. Minetti C. Vigevano F. (2006 ). A novel SCN2A mutation in family with benign familial infantile seizures. Epilepsia 47, 218–220.
Not in our library10.1111/j.1528-1167.2006.00392.x
277.
Su D. J. Lu J. F. Lin L. J. Liang J. S. Hung K. L. (2018 ). SCN2A mutation in an infant presenting with migrating focal seizures and infantile spasm responsive to a ketogenic diet. Brain Dev. 40, 724–727.
Not in our library10.1016/j.braindev.2018.03.005
278.
Sugawara T. Mazaki-Miyazaki E. Fukushima K. Shimomura J. Fujiwara T. Hamano S. (2002 ). Frequent mutations of SCN1A in severe myoclonic epilepsy in infancy. Neurology 58, 1122–1124.
Not in our library10.1212/wnl.58.7.1122
279.
Sugiura Y. Ogiwara I. Hoshi A. Yamakawa K. Ugawa Y. (2012 ). Different degrees of loss of function between GEFS+ and SMEI Na v1.1 missense mutants at the same residue induced by rescuable folding defects. Epilepsia 53, 111–114.
Not in our library10.1111/j.1528-1167.2012.03467.x
280.
Sun G. Werkman T. R. Battefeld A. Clare J. J. Wadman W. J. (2007 ). Carbamazepine and Topiramate Modulation of Transient and Persistent Sodium Currents Studied in HEK293 Cells Expressing the Na v 1.3?? Subunit. Epilepsia 48, 774–782.
Not in our library10.1111/j.1528-1167.2007.01001.x
281.
Sun H. Zhang Y. Liang J. Liu X. Ma X. Qin J. (2008 ). Seven novel SCN1A mutations in Chinese patients with severe myoclonic epilepsy of infancy. Epilepsia 49, 1104–1107.
Not in our library10.1111/j.1528-1167.2008.01549_2.x
282.
Sun H. Zhang Y. Liu X. Ma X. Yang Z. Qin J. (2010 ). Analysis of SCN1A mutation and parental origin in patients with Dravet syndrome. J. Hum. Genet. 55, 421–427.
Not in our library10.1038/jhg.2010.39
283.
Sun W. Wagnon J. L. Mahaffey C. L. Briese M. Ule J. Frankel W. N. (2013 ). Aberrant sodium channel activity in the complex seizure disorder of Celf4 mutant mice. J. Physiol. 591, 241–255.
Not in our library10.1113/jphysiol.2012.240168
284.
Syrbe S. Zhorov B. S. Bertsche A. Bernhard M. K. Hornemann F. Mütze U. (2016 ). Phenotypic Variability from Benign Infantile Epilepsy to Ohtahara Syndrome Associated with a Novel Mutation in SCN2A. Mol. Syndromol. 7, 182–188.
Not in our library10.1159/000447526
285.
Tai C. Abe Y. Westenbroek R. E. Scheuer T. Catterall W. A. (2014 ). Impaired excitability of somatostatin- and parvalbumin-expressing cortical interneurons in a mouse model of Dravet syndrome. Proc. Natl. Acad. Sci. U. S. A. 111, 3139–3148.
Not in our library10.1073/pnas.1411131111
286.
Takahashi S. Yamamoto S. Okayama A. Araki A. Saitsu H. Matsumoto N. (2015 ). Electroclinical features of epileptic encephalopathy caused by SCN8A mutation. Pediatr. Int. 57, 758–762.
Not in our library10.1111/ped.12622
287.
Tan N.-N. Tang H.-L. Lin G.-W. Chen Y.-H. Lu P. Li H.-J. (2017 ). Epigenetic Downregulation of Scn3a Expression by Valproate: a Possible Role in Its Anticonvulsant Activity. Mol. Neurobiol. 54, 2831–2842.
Not in our library10.1007/s12035-016-9871-9
288.
Thijs R. D. Surges R. O’Brien T. J. Sander J. W. (2019 ). Epilepsy in adults. Lancet 393, 689–701.
Not in our library10.1016/s0140-6736(18)32596-0
289.
Thomas R. H. Berkovic S. F. (2014 ). The hidden genetics of epilepsy – A clinically important new paradigm. Nat. Rev. Neurol. 10, 283–292.
Not in our library10.1038/nrneurol.2014.62
290.
Tibery D. V. Campos L. A. Mourão C. B. F. Peigneur S. Tytgat J. Schwartz E. F. (2019 ). Electrophysiological characterization of Tityus obscurus b toxin 1 (To1) on Na+-channel isoforms. Biochim. Biophys. Acta - Biomembr. 1861, 142–150.
Not in our library10.1016/j.bbamem.2018.08.005
291.
Tiefes A. M. Hartlieb T. Tacke M. von Stülpnagel-Steinbeis C. Larsen L. H. G. Hao Q. (2019 ). Mesial Temporal Sclerosis in SCN1A -Related Epilepsy: Two Long-Term EEG Case Studies. Clin. EEG Neurosci. 50, 267–272.
Not in our library10.1177/1550059418794347
292.
Tonekaboni S. H. Ebrahimi A. Bakhshandeh Bali M. K. Taheri Otaghsara S. M. Houshmand M. Nasehi M. M. (2013 ). Sodium channel gene mutations in Children with GEFS+ and Dravet syndrome: A cross sectional study. Iran. J. Child Neurol. 7, 31–36.
Not in our library10.22037/ijcn.v7i2.4074
293.
Trivisano M. Pavia G. C. Ferretti A. Fusco L. Vigevano F. Specchio N. (2019 ). Generalized tonic seizures with autonomic signs are the hallmark of SCN8A developmental and epileptic encephalopathy. Epilepsy Behav. 96, 219–223.
Not in our library10.1016/j.yebeh.2019.03.043
294.
Clinical exome sequencing: results from 2819 samples reflecting 1000 families · 2016
No notice
295.
Improving diagnosis and broadening the phenotypes in early-onset seizure and severe developmental delay disorders through gene panel analysis · 2016
No notice
296.
Tsang M. H.-Y. Leung G. K.-C. Ho A. C.-C. Yeung K.-S. Mak C. C.-Y. Pei S. L.-C. (2019 ). Exome sequencing identifies molecular diagnosis in children with drug-resistant epilepsy. Epilepsia Open 4, 63–72.
Not in our library10.1002/epi4.12282
297.
U.S. Food and Drug Administration [website] (2018 ). FDA Approves First Drug Comprised of an Active Ingredient Derived from Marijuana to Treat Rare, Severe Forms of Epilepsy. Available at: https://www.fda.gov/news-events/pressannouncements/fda-approves-first-drug-comprised-active-ingredientderived-marijuana-treat-rare-severe-forms (Accessed March 7, 2020).
Not in our library
298.
Usluer S. Salar S. Arslan M. Yiş U. Kara B. Tektürk P. (2016 ). SCN1A gene sequencing in 46 Turkish epilepsy patients disclosed 12 novel mutations. Seizure 39, 34–43.
Not in our library10.1016/j.seizure.2016.05.008
299.
Vaher U. Nõukas M. Nikopensius T. Kals M. Annilo T. Nelis M. (2013 ). De Novo SCN8A Mutation Identified by Whole-Exome Sequencing in a Boy With Neonatal Epileptic Encephalopathy, Multiple Congenital Anomalies, and Movement Disorders. J. Child Neurol. 29, NP202–NP206.
Not in our library10.1177/0883073813511300
300.
Vanoye C. G. Gurnett C. A. Holland K. D. George A. L. Kearney J. A. (2014 ). Novel SCN3A variants associated with focal epilepsy in children. Neurobiol. Dis. 62, 313–322.
Not in our library10.1016/j.nbd.2013.10.015
301.
Vecchi M. Cassina M. Casarin A. Rigon C. Drigo P. De Palma L. (2011 ). Infantile epilepsy associated with mosaic 2q24 duplication including SCN2A and SCN3A. Seizure 20, 813–816.
Not in our library10.1016/j.seizure.2011.07.008
302.
Veeramah K. R. O’Brien J. E. Meisler M. H. Cheng X. Dib-Hajj S. D. Waxman S. G. (2012 ). De novo pathogenic SCN8A mutation identified by whole-genome sequencing of a family quartet affected by infantile epileptic encephalopathy and SUDEP. Am. J. Hum. Genet. 90, 502–510.
Not in our library10.1016/j.ajhg.2012.01.006
303.
Veeramah K. R. Johnstone L. Karafet T. M. Wolf D. Sprissler R. Salogiannis J. (2013 ). Exome sequencing reveals new causal mutations in children with epileptic encephalopathies. Epilepsia 54, 1270–1281.
Not in our library10.1111/epi.12201
304.
Verbeek N. E. van Kempen M. Gunning W. B. Renier W. O. Westland B. Lindhout D. (2011 ). Adults with a history of possible Dravet syndrome: An illustration of the importance of analysis of the SCN1A gene. Epilepsia 52, e23–e25.
Not in our library10.1111/j.1528-1167.2011.02982.x
305.
Verbeek N. E. van der Maas N. A. T. Jansen F. E. van Kempen M. J. A. Lindhout D. Brilstra E. H. (2013 ). Prevalence of SCN1A-Related Dravet Syndrome among Children Reported with Seizures following Vaccination: A Population-Based Ten-Year Cohort Study. PloS One 8, e65758.
Not in our library10.1371/journal.pone.0065758
306.
Verret L. Mann E. O. Hang G. B. Barth A. M. I. I. Cobos I. Ho K. (2012 ). Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in alzheimer model. Cell 149, 708–721.
Not in our library10.1016/j.cell.2012.02.046
307.
Villeneuve N. Laguitton V. Viellard M. Lépine A. Chabrol B. Dravet C. (2014 ). Cognitive and adaptive evaluation of 21 consecutive patients with Dravet syndrome. Epilepsy Behav. 31, 143–148.
Not in our library10.1016/j.yebeh.2013.11.021
308.
Volkers L. Kahlig K. M. Verbeek N. E. Das J. H. G. van Kempen M. J. A. Stroink H. (2011 ). Na v1.1 dysfunction in genetic epilepsy with febrile seizures-plus or Dravet syndrome. Eur. J. Neurosci. 34, 1268–1275.
Not in our library10.1111/j.1460-9568.2011.07826.x
309.
Wagnon J. L. Meisler M. H. (2015 ). Recurrent and non-recurrent mutations of SCN8A in epileptic encephalopathy. Front. Neurol. 6, 104.
Not in our library10.3389/fneur.2015.00104
310.
Wagnon J. L. Barker B. S. Hounshell J. A. Haaxma C. A. Shealy A. Moss T. (2016 ). Pathogenic mechanism of recurrent mutations of SCN8A in epileptic encephalopathy. Ann. Clin. Transl. Neurol. 3, 114–123.
Not in our library10.1002/acn3.276
311.
Wagnon J. L. Barker B. S. Ottolini M. Park Y. Volkheimer A. Valdez P. (2017 ). Loss-of-function variants of SCN8A in intellectual disability without seizures. Neurol. Genet. 3, e170.
Not in our library10.1212/nxg.0000000000000170
312.
Wallace R. H. Scheffer I. E. Barnett S. Richards M. Dibbens L. Desai R. R. (2001 ). Neuronal sodium-channel β1-subunit mutations in generalized epilepsy with febrile seizures plus. Am. J. Hum. Genet. 68, 859–865.
Not in our library10.1086/319516
313.
Wang J. W. Shi X. Y. Kurahashi H. Hwang S. K. Ishii A. Higurashi N. (2012 ). Prevalence of SCN1A mutations in children with suspected Dravet syndrome and intractable childhood epilepsy. Epilepsy Res. 102, 195–200.
Not in our library10.1016/j.eplepsyres.2012.06.006
314.
Wang J. Gao H. Bao X. Zhang Q. Li J. Wei L. (2017 a). SCN8A mutations in Chinese patients with early onset epileptic encephalopathy and benign infantile seizures. BMC Med. Genet. 18, 104.
Not in our library10.1186/s12881-017-0460-1
315.
Wang Y. Du X. Bin R. Yu S. Xia Z. Zheng G. (2017 b). Genetic Variants Identified from Epilepsy of Unknown Etiology in Chinese Children by Targeted Exome Sequencing. Sci. Rep. 7, 40319.
Not in our library10.1038/srep40319
316.
Waxman S. G. Hains B. C. (2006 ). Fire and phantoms after spinal cord injury: Na+ channels and central pain. Trends Neurosci. 29, 207–215.
Not in our library10.1016/j.tins.2006.02.003
317.
Weber Y. G. Nies A. T. Schwab M. Lerche H. (2014 ). Genetic Biomarkers in Epilepsy. Neurotherapeutics 11, 324–333.
Not in our library10.1007/s13311-014-0262-5
318.
Weiss L. A. Escayg A. Kearney J. A. Trudeau M. MacDonald B. T. Mori M. (2003 ). Sodium channels SCN1A, SCN2A and SCN3A in familial autism. Mol. Psychiatry 8, 186–194.
Not in our library10.1038/sj.mp.4001241
319.
Wengert E. R. Tronhjem C. E. Wagnon J. L. Johannesen K. M. Petit H. Krey I. (2019 ). Biallelic inherited SCN8A variants, a rare cause of SCN8A -related developmental and epileptic encephalopathy. Epilepsia 60, 2277–2285.
Not in our library10.1111/epi.16371
320.
NaV1.1 and NaV1.6 selective compounds reduce the behavior phenotype and epileptiform activity in a novel zebrafish model for Dravet Syndrome. · 2020
Not checked
321.
Whitaker W. R. J. Clare J. J. Powell A. J. Chen Y. H. Faull R. L. M. Emson P. C. (2000 ). Distribution of voltage-gated sodium channel?-subunit and?-subunit mRNAs in human hippocampal formation, cortex, and cerebellum. J. Comp. Neurol. 422, 123–139.
Not in our library10.1002/(sici)1096-9861(20000619)422:1<123::aid-cne8>3.0.co;2-x
322.
Willemsen M. H. Rensen J. H. M. van Schrojenstein-Lantman de Valk H. M. J. Hamel B. C. J. Kleefstra T. (2012 ). Adult Phenotypes in Angelman- and Rett-Like Syndromes. Mol. Syndromol. 2, 217–234.
Not in our library10.1159/000335661
323.
Wittmack E. K. Rush A. M. Craner M. J. Goldfarb M. Waxman S. G. Dib-Hajj S. D. (2004 ). Fibroblast growth factor homologous factor 2B: Association with Na v1.6 and selective colocalization at nodes of Ranvier of dorsal root axons. J. Neurosci. 24, 6765–6775.
Not in our library10.1523/jneurosci.1628-04.2004
324.
Wolff M. Johannesen K. M. Hedrich U. B. S. Masnada S. Rubboli G. Gardella E. (2017 ). Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders. Brain 140, 1316–1336.
Not in our library10.1093/brain/awx054
325.
Wong V. C. N. Fung C. W. Kwong A. K. Y. (2015 ). SCN2A mutation in a Chinese boy with infantile spasm - response to Modified Atkins Diet. Brain Dev. 37, 729–732.
Not in our library10.1016/j.braindev.2014.10.008
326.
Wu Y. W. Sullivan J. McDaniel S. S. Meisler M. H. Walsh E. M. Li S. X. (2015 ). Incidence of dravet syndrome in a US population. Pediatrics 136, e1310–e1315.
Not in our library10.1542/peds.2015-1807
327.
Wu Q. Wang H. Fan Y. Y. Zhang J. M. Liu X. Y. Fang X. Y. (2018 ). Ketogenic diet effects on 52 children with pharmacoresistant epileptic encephalopathy: A clinical prospective study. Brain Behav. 8, 1–8.
Not in our library10.1002/brb3.973
328.
Xiao Y. Xiong J. Mao D. Liu L. Li J. Li X. (2018 ). Early-onset epileptic encephalopathy with de novo SCN8A mutation. Epilepsy Res. 139, 9–13.
Not in our library10.1016/j.eplepsyres.2017.10.017
329.
Xie H. Su W. Pei J. Zhang Y. Gao K. Li J. (2019 ). De novo SCN1A, SCN8A, and CLCN2 mutations in childhood absence epilepsy. Epilepsy Res. 154, 55–61.
Not in our library10.1016/j.eplepsyres.2019.04.005
330.
Xu R. Thomas E. A. Gazina E. V. Richards K. L. Quick M. Wallace R. H. (2007 ). Generalized epilepsy with febrile seizures plus-associated sodium channel β1 subunit mutations severely reduce beta subunit-mediated modulation of sodium channel function. Neuroscience 148, 164–174.
Not in our library10.1016/j.neuroscience.2007.05.038
331.
Xu X. Zhang Y. Sun H. Liu X. Yang X. Xiong H. (2014 ). Early clinical features and diagnosis of Dravet syndrome in 138 Chinese patients with SCN1A mutations. Brain Dev. 36, 676–681.
Not in our library10.1016/j.braindev.2013.10.004
332.
Xu X. Yang X. Wu Q. Liu A. Yang X. Ye A. Y. (2015 ). Amplicon Resequencing Identified Parental Mosaicism for Approximately 10% of “ de novo “ SCN1A Mutations in Children with Dravet Syndrome. Hum. Mutat. 36, 861–872.
Not in our library10.1002/humu.22819
333.
Yan N. Xin-Hua W. Lin-Mei Z. Yi-Ming C. Wen-Hui L. Yuan-Feng Z. (2018 ). Prospective study of the efficacy of a ketogenic diet in 20 patients with Dravet syndrome. Seizure 60, 144–148.
Not in our library10.1016/j.seizure.2018.06.023
334.
Yang Y.-C. Huang C.-S. Kuo C.-C. (2010 ). Lidocaine, Carbamazepine, and Imipramine Have Partially Overlapping Binding Sites and Additive Inhibitory Effect on Neuronal Na+ Channels. Anesthesiology 113, 160–174.
Not in our library10.1097/aln.0b013e3181dc1dd6
335.
Yang X. Liu A. Xu X. Yang X. Zeng Q. Ye A. Y. (2017 ). Genomic mosaicism in paternal sperm and multiple parental tissues in a Dravet syndrome cohort. Sci. Rep. 7, 15677.
Not in our library10.1038/s41598-017-15814-7
336.
Yang C. Hua Y. Zhang W. Xu J. Xu L. Gao F. (2018 ). Variable epilepsy phenotypes associated with heterozygous mutation in the SCN9A gene: report of two cases. Neurol. Sci. 39, 1113–1115.
Not in our library10.1007/s10072-018-3300-y
337.
Yordanova I. Todorov T. Dimova P. Hristova D. Tincheva R. Litvinenko I. (2011 ). One novel Dravet syndrome causing mutation and one recurrent MAE causing mutation in SCN1A gene. Neurosci. Lett. 494, 180–183.
Not in our library10.1016/j.neulet.2011.03.008
338.
Young F. (2007 ). When adaptive processes go awry: gain-of-function in SCN9A. Clin. Genet. 73, 34–36.
Not in our library10.1111/j.1399-0004.2007.00922.x
339.
Yu F. H. Mantegazza M. Westenbroek R. E. Robbins C. A. Kalume F. Burton K. A. (2006 ). Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy. Nat. Neurosci. 9, 1142–1149.
Not in our library10.1038/nn1754
340.
Yu M.-J. Shi Y.-W. Gao M.-M. Deng W.-Y. Liu X.-R. Chen L. (2010 ). Milder phenotype with SCN1A truncation mutation other than SMEI. Seizure 19, 443–445.
Not in our library10.1016/j.seizure.2010.06.010
341.
Zaman T. Helbig I. Božović I. B. DeBrosse S. D. Bergqvist A. C. Wallis K. (2018 ). Mutations in SCN3A cause early infantile epileptic encephalopathy. Ann. Neurol. 83, 703–717.
Not in our library10.1002/ana.25188
342.
Zaman T. Abou Tayoun A. Goldberg E. M. (2019 ). A single-center SCN8A- related epilepsy cohort: clinical, genetic, and physiologic characterization. Ann. Clin. Transl. Neurol. 6.. acn3.50839.
Not in our library10.1002/acn3.50839
343.
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.
Not in our library10.1111/epi.12089
344.
Zhang X. Ren W. Decaen P. Yan C. Tao X. Tang L. (2012 ). Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel. Nature 486, 130–135.
Not in our library10.1038/nature11054
345.
Zhang Y. Kong W. Gao Y. Liu X. Gao K. Xie H. (2015 ). Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities. PloS One 10, e0141782.
Not in our library10.1371/journal.pone.0141782
346.
Zhang S. Zhang Z. Shen Y. Zhu Y. Du K. Guo J. (2020 ). SCN9A Epileptic Encephalopathy Mutations Display a Gain-of-function Phenotype and Distinct Sensitivity to Oxcarbazepine. Neurosci. Bull. 36, 11–24.
Not in our library10.1007/s12264-019-00413-5
347.
Zhang F. Wu Y. Zou X. Tang Q. Zhao F. Cao Z. (2019 ). BmK AEP, an Anti-Epileptic Peptide Distinctly Affects the Gating of Brain Subtypes of Voltage-Gated Sodium Channels. Int. J. Mol. Sci. 20, 729.
Not in our library10.3390/ijms20030729
348.
Zhang T. Chen M. Zhu A. Zhang X. Fang T. (2020 ). Novel mutation of SCN9A gene causing generalized epilepsy with febrile seizures plus in a Chinese family. Neurol. Sci. 41, 1913–1917.
Not in our library10.1007/s10072-020-04284-x
349.
Zhou P. He N. Zhang J. W. Lin Z. J. Wang J. Yan L. M. (2018 ). Novel mutations and phenotypes of epilepsy-associated genes in epileptic encephalopathies. Genes Brain Behav. 17, e12456.
Not in our library10.1111/gbb.12456
350.
Ziobro J. Eschbach K. Sullivan J. E. Knupp K. G. (2018 ). Current Treatment Strategies and Future Treatment Options for Dravet Syndrome. Curr. Treat. Options Neurol. 20, 1–15.
Not in our library10.1007/s11940-018-0537-y
351.
Zuberi S. M. Brunklaus A. Birch R. Reavey E. Duncan J. Forbes G. H. (2011 ). Genotype-phenotype associations in SCN1A-related epilepsies. Neurology 76, 594–600.
Not in our library10.1212/wnl.0b013e31820c309b
352.
Zucca C. Redaelli F. Epifanio R. Zanotta N. Romeo A. Lodi M. (2008 ). Cryptogenic Epileptic Syndromes Related to SCN1A. Arch. Neurol. 65, 489.
Not in our library10.1001/archneur.65.4.489

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.