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This study aims to describe the main cognitive and behavioral comorbidities of Dravet syndrome (DS) and Lennox–Gastaut syndrome (LGS), their impact on the health-related quality of life (QOL) of patients and their caregivers, and provide a summary of the neuropsychological tools available for the evaluation of these comorbidities. The cognitive and behavioral comorbidities in patients with DS and LGS have a profound effect on the QOL of affected individuals and their caregivers and, as patients grow, tend to surpass the impact of the seizures. DS is a genetic condition associated with loss-of-function mutations in the SCNA1 sodium channel gene; LGS is an etiologically heterogeneous condition that is often secondary to structural brain abnormalities. The first seizures associated with DS typically present in the first year of life, and developmental delay becomes progressively evident thereafter. LGS usually starts between the ages of 3 and 8 years, with cognitive impairment becoming clinically evident in most patients within 5 years from the onset. In both DS and LGS, cognitive impairment is generally moderate to severe and is often accompanied by behavioral problems such as hyperactivity and inattention. In addition to optimal seizure control, regular assessment and active management of cognitive and behavioral comorbidities are required to meet the complex needs of patients with DS or LGS.

A total of 2809 ixodid ticks were collected by screening 4560 household cattle from six different agro-climatic zones of Tamil Nadu, a southern state of India. Among the ixodid ticks, Rhipicephalus microplus tick isolates were subjected to Adult Immersion Test (AIT) and Larval Packet Test (LPT) using deltamethrin. The mean % of ixodid tick infested cattle population was 63.2%±10.9. Positive correlation was found between the tick burden on household cattle and Resistance Factor (R=0.66). Further, 44% variance in the tick burden on cattle is explained by LPT based resistance factor suggesting deltamethrin resistance level is one of the contributing factors to the tick load on cattle. Analysis of DNA sequence of sodium channel gene domain II-S4-5 linker region of all deltamethrin resistant R. microplus tick isolates, confirmed the absence of point mutation at the 190th nucleotide which suggests the possible mutation in other regions of sodium channel gene of R. microplus tick isolates of south India and/or alternate resistance mechanisms.

Background: Genetics research of humans has established that a genetic basis contributes to the susceptibility to epilepsy for a majority of the cases. Although many epilepsies are secondary to injury or another illness, approximately 40% are idiopathic, meaning that the original cause is unknown. It is presumed that most idiopathic epilepsies result from genetic abnormalities, with the majority likely caused by mutations in multiple currently unidentified genes. However, research has revealed a growing number of single-gene mutations that cause epilepsy. Objective: To detect some of the genetic mutations which may cause idiopathic epilepsy. Methods: The current study is a cross-sectional study that had been performed at Sheikh Mohamed Khair center, Banat, Omdurman, and National Centre for Neurological Sciences (NCNS) Khartoum state, during the period 2016 to 2019. Ninety-nine participants were enrolled in this study. Demographic data were collected in a predesigned questionnaire blood samples were analyzed for biochemical and molecular tests. Results: Ninety-nine patients diagnosed with idiopathic epilepsy were recruited in this study. The most affected age group was 18 - 40 years accounted for 55% of patients. Females were the majority with 53%. Fifty percent of the patients had the first seizure at age less than 5 years. Ninety percent of the patients have no Family history with epilepsy. All sequenced samples showed genetic mutations, deletion mutation was detected in 71% of the samples. Bioinformatics tools detected a frameshift mutation in the chain of the amino acids. Conclusion: The current study detected deletion mutations in SCN1A gene (frameshift) can cause epilepsy by changing some amino acids with residues that can affect neuronal stability indirectly.

RESUMEN Las mutaciones KDR en el gen del canal del sodio (VGSC) han sido ya detectadas en al menos 13 especies de mosquitos Anopheles en su mayoría especies de África, pero aún resta por determinar los cebadores específicos para la detección en especies de Latinoamérica. En nuestro país la especie Anopheles darlingi es el vector principal de la malaria, y el A. albitarsis, el vector secundario. Se emplearon muestras de mosquitos Anoheles de las especies A. strodei, A. albitarsis, A. fluminensis, A. evansae, A. nuneztovari, A. nyssorhynchela lutzi y A. oswaldoi capturadas en los departamentos de Caaguazú y Alto Paraná en Paraguay. Para la amplificación y secuenciación se usaron cebadores reportados para el gen VGSC de A. albimanus en Guatemala, que resultaron ser específicos solo para la especie A. strodei. La secuencia revela el codón TTA que codifica para una Leucina como la secuencia TTG, reportada para la versión susceptible en la posición L1014. El fragmento amplificado es de aproximadamente 225 pares de bases. A nuestro entender, esta es la primera caracterización del gen VGSC en mosquitos Anopheles del Paraguay y para la especie A. strodei. ABSTRACT KDR mutations in the sodium channel gene (VGSC) have already been detected in at least 13 species of Anopheles mosquitoes, mostly African species, but the molecular techniques for detection in Latin American species have yet to be determined. In our country, Anopheles darlingi species is the main vector of Malaria, and A. albitarsis, the secondary vector. We used samples of Anoheles from the species A. strodei, A. albitarsis, A. fluminensis, A. evansae, A. nuneztovari, A. nyssorhynchela lutzi and A. oswaldoi collected at the departments of Caaguazú and Alto Paraná in Paraguay. For the amplification and sequentiation, primers reported for the VGSC gen of A. strodei in Guatemala were used and were specific only for A. strode in this case. The sequence revealed the TTA codon that codifies for a leucine as the TTG sequence, reported for the susceptible version at position L1014. The amplified fragment is approximately 225 base pairs. To our knowledge, this is the first characterization of the VGSC gene in Anopheles mosquitoes in Paraguay and for the species A. strodei.

Mutations in numerous genes which encode for voltage-gated sodium channels give rise to various epilepsy syndromes in humans. Our research investigation mainly focuses on the identification of the integral membrane protein of the SCN1A (Sodium Voltage-Gated Channel Alpha Subunit 1) in humans. Secondary, we focus on the transmembrane membrane (TP) amino acids directly involved in the epilepsy-involved mutated regions. Using Insilico protocols, we identify the TP proteins and amino acids and elucidate the Transmembrane Helix and the inside and outside amino acids regions of the SCN1A. With the help of Insilico proteomics server, the amino acids in the mutated regions involved in the TP were identified. Finally, 3D structure prediction was performed using homology modelling server and the modelled structure was cross validated for the TP and validated. The identified results were validated using molecular visualization tools. We prove that the mutated amino acids are present in the outer membrane of the TP regions. Thus, the outer membrane of sodium channel and the amino acids present in the outer membrane (T875M, R859C, and R1648H) play a vital role in Structure-Based Drug Designing and Drug Docking studies.

dCas9-Based Scn1a Gene Activation Restores Inhibitory Interneuron Excitability and Attenuates Seizures in Dravet Syndrome MiceColasante G, Lignani G, Brusco S, et al. Mol Ther. 2020;28(1):235-253. doi:10.1016/j.ymthe.2019.08.018Dravet syndrome (DS) is a severe epileptic encephalopathy caused mainly by heterozygous loss-of-function mutations of the SCN1A gene, indicating haploinsufficiency as the pathogenic mechanism. Here, we tested whether catalytically dead Cas9 (dCas9)-mediated Scn1a gene activation can rescue Scn1a haploinsufficiency in a mouse DS model and restore physiological levels of its gene product, the Nav1.1 voltage-gated sodium channel. We screened single guide RNAs (sgRNAs) for their ability to stimulate Scn1a transcription in association with the dCas9 activation system. We identified a specific sgRNA that increases Scn1a gene expression levels in cell lines and primary neurons with high specificity. Nav1.1 protein levels were augmented, as was the ability of wild-type immature GABAergic interneurons to fire action potentials. A similar enhancement of Scn1a transcription was achieved in mature DS interneurons, rescuing their ability to fire. To test the therapeutic potential of this approach, we delivered the Scn1a-dCas9 activation system to DS pups using adeno-associated viruses. Parvalbumin interneurons recovered their firing ability, and febrile seizures were significantly attenuated. Our results pave the way for exploiting dCas9-based gene activation as an effective and targeted approach to DS and other disorders resulting from altered gene dosage.Scn8a Antisense Oligonucleotide Is Protective in Mouse Models of SCN8A Encephalopathy and Dravet syndromeLenk GM, Jafar Nejad P, Hill SF, et al. Ann Neurol. 2020;87(3):339-346. doi:10.1002/ana.25676SCN8A encephalopathy is a developmental and epileptic encephalopathy caused by de novo gain-of-function mutations of sodium channel Nav 1.6 that result in neuronal hyperactivity. Affected individuals exhibit early-onset drug-resistant seizures, developmental delay, and cognitive impairment. This study was carried out to determine whether reducing the abundance of the Scn8a transcript with an antisense oligonucleotide (ASO) would delay seizure onset and prolong survival in a mouse model of SCN8A encephalopathy. Antisense oligonucleotide treatment was tested in a conditional mouse model with Cre-dependent expression of the pathogenic patient SCN8A mutation p.Arg1872Trp (R1872 W). This model exhibits early onset of seizures, rapid progression, and 100% penetrance. An Scn1a+/− haploinsufficient mouse model of Dravet syndrome was also treated. Antisense oligonucleotide was administered by intracerebroventricular injection at postnatal day 2, followed in some cases by stereotactic injection at postnatal day 30. We observed a dose-dependent increase in length of survival from 15 to 65 days in the Scn8a-R1872W/+ mice treated with ASO. Electroencephalographic recordings were normal prior to seizure onset. Weight gain and activity in an open field were unaffected, but treated mice were less active in a wheel running assay. A single treatment with Scn8a ASO extended survival of Dravet syndrome mice from 3 weeks to >5 months. Reduction of Scn8a transcript by 25% to 50% delayed seizure onset and lethality in mouse models of SCN8A encephalopathy and Dravet syndrome. Reduction of SCN8A transcript is a promising approach to treatment of intractable childhood epilepsies.

Introduction Mutations of the voltage-gated sodium channel gene (SCN4A), which encodes Nav1.4, cause nondystrophic myotonia that occasionally is associated with severe apnea and laryngospasm. There are case reports of nondystrophic myotonia due to mutations in the C-terminal tail (CTerm) of Nav1.4, but the functional analysis is scarce. Methods We present two families with nondystrophic myotonia harboring a novel heterozygous mutation (E1702del) and a known heterozygous mutation (E1702K). Results The proband with E1702K exhibited repeated rhabdomyolysis, and the daughter showed laryngospasm and cyanosis. Functional analysis of the two mutations as well as another known heterozygous mutation (T1700_E1703del), all located on EF hand-like motif in CTerm, was conducted with whole-cell recording of heterologously expressed channel. All mutations displayed impaired fast inactivation. Discussion The CTerm of Nav1.4 is vital for regulating fast inactivation. The study highlights the importance of accumulating pathological mutations of Nav1.4 and their functional analysis data.

Dravet syndrome is a genetic developmental and epileptic encephalopathy (DEE) mostly due to mutations in SCN1A gene. Perampanel is a selective and non-competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist. There is increasing experience in the use of perampanel in this syndrome; however, there is still a lack of evidence of sustained benefit years after the beginning of the treatment. We report a twelve-year-old girl who was diagnosed with Dravet Syndrome when she was 2 years old and has been on perampanel since she was 7. Her genetic test showed a de novo previously described heterozygous SCN1A mutation in the 24th exon (c.4547C>A, p.Ser1516*). She received previous antiseizure drug combinations with little benefit. When perampanel was started, there was a complete resolution of her spontaneous seizures that has continued five years later. More studies are needed to investigate if there is an association between this excellent response and the genotype of our patient.

Background Many antiseizure medications (ASMs) control seizures by blocking voltage-dependent sodium channels. Polymorphisms of sodium channel genes may affect the response to ASMs due to altering the effect of ASMs on blocking sodium channels. Methods We conducted a retrospective study of epilepsy patients followed up at the Neurological Department of Kaohsiung Chang Gung Memorial Hospital, Taiwan between January 2010 and December 2018. We categorized the patients into response, partial response, and failure to sodium channel blocking ASM groups. Sodium channel blocking ASMs included phenytoin, carbamazepine, lamotrigine, oxcarbazepine, lacosamide, zonisamide, topiramate, and valproic acid. A subgroup of predominant sodium channel blocking ASMs included phenytoin, carbamazepine, lamotrigine, oxcarbazepine, and lacosamide. Associations between the response of ASMs and single-nucleotide polymorphisms of SCN1A, SCN1B, SCN2A, and SCN9A were analyzed. Results Two hundred Taiwanese patients and 21 single-nucleotide polymorphisms among SCN1A, SCN1B, SCN2A, and SCN9A were evaluated. We found allele C of rs55742440 in SCN1B was statistically significantly associated with not achieving seizure-free with sodium channel blocking ASMs. For the predominant sodium channel blocking ASMs group, no SNPs were associated with the response of ASMs. Conclusion Single-nucleotide polymorphism in SCN1B was associated with the response to sodium channel blocking ASMs. This highlights the possibility that beta subunits may affect the function of sodium channels and resulted in different responsiveness to ASMs.

Background Volatile pyrethroid insecticides, such as transfluthrin, have received increasing attention for their potent repellent activities in recent years for controlling human disease vectors. It has been long understood that pyrethroids kill insects by promoting activation and inhibiting inactivation of voltage-gated sodium channels. However, the mechanism of pyrethroid repellency remains poorly understood and controversial. Methodology/Principal findings Here, we show that transfluthrin repels Aedes aegypti in a hand-in-cage assay at nonlethal concentrations as low as 1 ppm. Contrary to a previous report, transfluthrin does not elicit any electroantennogram (EAG) responses, indicating that it does not activate olfactory receptor neurons (ORNs). The 1S-cis isomer of transfluthrin, which does not activate sodium channels, does not elicit repellency. Mutations in the sodium channel gene that reduce the potency of transfluthrin on sodium channels decrease transfluthrin repellency but do not affect repellency by DEET. Furthermore, transfluthrin enhances DEET repellency. Conclusions/Significance These results provide a surprising example that sodium channel activation alone is sufficient to potently repel mosquitoes. Our findings of sodium channel activation as the principal mechanism of transfluthrin repellency and potentiation of DEET repellency have broad implications in future development of a new generation of dual-target repellent formulations to more effectively repel a variety of human disease vectors., Author summary Vector-transmitted human diseases, such as dengue fever, represent serious global health burdens. Pyrethroids, including transfluthrin, are widely used as insecticides and repellents due to their low mammalian toxicity and relatively benign environmental impact. Pyrethroids target voltage-gated sodium channels for their insecticidal action. However, the mechanism of pyrethroid repellency remains unclear and controversial. Insect repellency is traditionally thought to be mediated by olfactory receptors. We made two important discoveries in this study, showing that transfluthrin repellency is via activation of sodium channels and transfluthrin enhances DEET repellency. Discovery of sodium channel activation as a major mechanism of pyrethroid repellency has broad significance in insect olfaction study, repellents development, and control of human disease vectors.

Dravet Syndrome (DS) is a severe childhood epilepsy caused by heterozygous loss-of-function mutations in the SCN1A gene encoding brain type-I voltage-gated sodium channel Nav1.1. DS is a devastating disease that typically begins at six to nine months of age. Symptoms include recurrent intractable seizures and premature death with severe neuropsychiatric comorbidities, including hyperactivity, sleep disorder, anxiety-like behaviors, impaired social interactions, and cognitive deficits. There is an urgent unmet need for therapeutic approaches that control and cure DS, as available therapeutic interventions have poor efficacy, intolerance, or other side effects. Here we investigated the therapeutic potential of combining the benzodiazepine clonazepam (CLZ) with the nonpsychotropic phytocannabinoid cannabidiol (CBD) against thermally induced febrile seizures in a conditional mouse model of DS. Our results show that a low dose of CLZ alone or combined with CBD elevated the threshold temperature for the thermal induction of seizures. Combination of CLZ with CBD significantly reduced seizure duration compared to the vehicle or CLZ alone, but did not affect seizure severity, indicating potential additive actions of CLZ and CBD on the duration of seizures. Our findings provide preclinical evidence supporting combination therapy of CLZ and CBD for treatment of febrile seizures in DS.

The Drosophila mutant paraShu harbors a dominant, gain-of-function allele of the voltage-gated sodium channel gene, paralytic (para). The mutant flies display severe seizure-like phenotypes...

In this report, we present the case of a one-year-old female patient with a history of febrile seizures, which was characterized by multiple seizures during hot baths and more than one episode of status epilepticus. Dravet syndrome was suspected due to the clinical context of the seizures and was confirmed by genetic testing. The brain MRI was found to be normal. Throughout the course of disease progression, the patient showed no signs of neurological degradation. The patient was found to have a mutation in the SCN1A gene with a peculiar course, which had not been reported previously. The normal psychomotor development, as seen in this case, highlights the different possibilities related to disease progression in Dravet syndrome.

Fishes have independently evolved electric organs (EOs) at least six times, and the electric fields are used for communication, defense, and predation. However, the genetic basis of convergent evolution of EOs remains unclear. In this study, we conducted comparative genomic analyses to detect genes showing signatures of positive selection and convergent substitutions in electric fishes from three independent lineages (Mormyroidea, Siluriformes, and Gymnotiformes). Analysis of 4,657 orthologs between electric fishes and their corresponding control groups identified consistent evidence for accelerated evolution in electric fish lineages. A total of 702 positively selected genes (PSGs) were identified in electric fishes, and many of these genes corresponded to cell membrane structure, ion channels, and transmembrane transporter activity. Comparative genomic analyses revealed that widespread convergent amino acid substitutions occurred along the electric fish lineages. The overlap of convergent genes and PSGs was identified as adaptive convergence, and a subset of genes was putatively associated with electrical and muscular activities, especially scn4aa (a voltage-gated sodium channel gene). Our results provide hints to the genetic basis for the independent evolution of EOs during millions of years of evolution.

Densitometric analysis is often used to quantify Na(V)1.1 protein on immunoblots, although the sensitivity and dilution linearity of the method are usually poor. Here we present a protocol for quantification of Na(V)1.1 in mouse brain tissues using a Meso Scale Discovery-Electrochemiluminescence (MSD-ECL) method. MSD-ECL is based on ELISA (enzyme-linked immunosorbent assay) and uses electrochemiluminescence to produce measurable signals. Two different antibodies are used in this assay to capture and detect Na(V)1.1 respectively in brain tissue lysate. The specificity of the antibodies is confirmed by Scn1a gene knock-out tissue. The calibration curve standards used in this assay were generated with mouse liver lysate spiked with mouse brain lysate, instead of using a recombinant protein. We showed that this method was qualified and used for quantification of Na(V)1.1 in mouse brain tissues with specificity, accuracy and precision.

The SCN5A gene, located on chromosome 3p21, has 28 exons and is a member of the human voltage-gated sodium channel gene family. Genetic variation in SCN5A is associated with a diverse range of phenotypes. Due to incomplete penetrance, delayed expression, inherent low signal-to-noise ratio, and marked phenotypic heterogeneity, rare novel variants in SCN5A could be misinterpreted. Hence, defining the phenotypic characteristics of these rare SCN5A variants in humans is of importance. We describe the phenotypic heterogeneity noted in 4 familial carriers of a rare, previously unreported, large deletion in exon 20 of SCN5A (c.3667-?_c.3840C +?del) and discuss the mechanisms that underlie this heterogeneity.

Background: ABCB1, EPHX1 and SCN1A gene polymorphisms have been reported play important roles in individual variability carbamazepine (CBZ) metabolism and resistance, but the result of that association still remains controversial. Objective: To clarify the associations among ABCB1, EPHX1 and SCN1A gene polymorphisms and CBZ metabolism and resistance. Methods: The PubMed, EMBASE, Cochrane library, Chinese National Knowledge Infrastructure, Chinese Science and Technique Journals Database, China Biology medicine disc and Wan Fang Database were searched for appropriate studies up to April 2020. Results: A total of 18 studies involving 3293 related epilepsy patients were included. ABCB1 c.3435C>T polymorphism was significantly associated with adjusted concentrations of CBZ (CC vs. CT, P=0.004), and EPHX c.416A>G polymorphism was significantly associated with carbamazepine-10, 11-trans dihydrodiol (CBZD) (AA vs. GG, P=0.045; AG vs. GG, P=0.010). Furthermore, ABCB1 c.3435C>T polymorphism was also observed to be significantly influenced CBZ resistance (CT vs TT, P=0.01; CC+CT vs TT, P=0.006). Conclusion: ABCB1 c.3435C>T polymorphism may affect the CBZ metabolism and resistance, EPHX1 c.416A>G polymorphism may only affect CBZ metabolism. These findings provided further evidence for individualized therapy of epilepsy patients in clinics. Nevertheless further large studies are still warranted to provide conclusive evidences.

Plakophilin-2 (PKP2) is the most frequently mutated desmosomal gene in arrhythmogenic cardiomyopathy (ACM), a disease characterized by structural and electrical alterations predominantly affecting the right ventricular myocardium. Notably, ACM cases without overt structural alterations are frequently reported, mainly in the early phases of the disease. Recently, the PKP2 p.S183N mutation was found in a patient affected by Brugada syndrome (BS), an inherited arrhythmic channelopathy most commonly caused by sodium channel gene mutations. We here describe a case of a patient carrier of the same BS-related PKP2 p.S183N mutation but with a clear diagnosis of ACM. Specifically, we report how clinical and molecular investigations can be integrated for diagnostic purposes, distinguishing between ACM and BS, which are increasingly recognized as syndromes with clinical and genetic overlaps. This observation is fundamentally relevant in redefining the role of genetics in the approach to the arrhythmic patient, progressing beyond the concept of “one mutation, one disease”, and raising concerns about the most appropriate approach to patients affected by structural/electrical cardiomyopathy. The merging of genetics, electroanatomical mapping, and tissue and cell characterization summarized in our patient seems to be the most complete diagnostic algorithm, favoring a reliable diagnosis.

The Brugada syndrome (BrS), one of the most devastating causes of sudden cardiac death in relatively young patients with apparently normal hearts, was originally termed in 1992. According to the recent consensus conference of J wave syndromes in 2016, only spontaneous type 1 Brugada-ECG pattern is the basis for the diagnosis of BrS. Mutations which affect cardiac ion currents have been linked to the syndrome, however strong evidence of link to the disease has been established only for the cardiac sodium channel gene SCN5A. Because all mutations thus far identified in SCN5A display an autosomal dominant mode of transmission, males and females would be expected to inherit the defective gene equally, however, Brugada-ECG pattern phenotype is 8 to 10 times more prevalent in men than in women. Moreover, malignant BrS is surprisingly uncommon in females, representing less than 10% of the patient population with arrhythmic events (AEs). This explains the difficulty of accurately comparing the clinical, ECG, electrophysiologic and genetic characteristics of males and females with BrS and AEs. In the present chapter we will review the main sex differences in BrS patients.

Voltage-gated sodium channels have been implicated in numerous inherited paroxysmal disorders of the nervous system, muscle, and heart. Our goal is to provide a framework that helps neurologists understand the clinical and treatment implications of sodium channel variants they encounter in clinical practice. This will be accomplished through our objectives of (1) recognizing the relationship between location of a missense sodium channel gene variant and its effect on channel function, and (2) categorizing clinical phenotype based on functional effect of a variant. The relationship between location, function, and treatment response is also discussed. These interactions can be illustrated by the sodium channelopathies seen in people with epilepsy but generalize beyond that disorder. Ann Neurol 2018;83:1-9.

Purpose "Single Nucleotide Polymorphisms (SNPs)" could be an important explanation of drug resistance in epilepsy. The aim of this study was to investigate if genetic polymorphisms (SNPs) of the SCN1A gene could influence the response to anti – epileptic drugs (AED) and if they could predispose to a drug resistant epilepsy in pediatric patients. Methods We investigated SNPs in exon and intronic regions of the SCN1A gene in a sample of 120 pediatric patients, in both drug-resistant and drug-responsive patients. Association between polymorphisms and refractory epilepsy were investigated by comparing SNPs in exon and intronic regions between the two groups. The genotypes of each intronic polymorphism in the drug-resistant group was analyzed. Odds ratios and confidence intervals were calculated. Results None of the SNPs identified in exons of the SCN1A gene were associated with drug-resistance. In the intronic regions, a statistically significant difference was found in the prevalence of three polymorphisms was found between the two patient groups (rs6730344A/C, rs6732655A/T, rs10167228A/T). The analysis of the genotypes of each intronic polymorphism in the drug-resistant group revealed that the AA and AT genotypes for the rs1962842 polymorphism are associated with an increased risk of developing drug resistance compared to TT genotype. Conclusion The intronic rs6730344, rs6732655 and rs10167228 polymorphisms of the SCN1A gene are a potential risk factors for drug resistance. AA e AT genotype of the rs1962842 intronic polymorphism also emerged as a risk factor in the drug resistant group. Therefore, polymorphisms of the SCN1A gene could play a role in the response to AED in patients with drug-resistant epilepsy, with important implications for clinical practice.

Febrile seizure is a common convulsions occur in children from 5 months to 6 years of age whose suffering from high temperature. A total of 50 children with febrile seizures and 50 normal control are included in this study. RFLP used to identify the A/G polymorphisms of the SCN1A gene on chromosome 2q24. Results showed that the genotype proportions and allele frequencies for SCN1A c.3184 A/G in both groups are not significantly. Proportions of A homozygote, A/G heterozygote, and G homozygote for SCN1A c.3184 A/G were as follows: in patients with FSs, 20%, 50%, and 30%, respectively compared to controls (24%, 62%, and 14%, respectively). The allele A and G frequencies for SCN1A c.3184 A/G in patients with FSs was 45% and 55% respectively compared to control group. The frequency of AG genotype of SCN1A c.3184 A/G polymorphism was non-significant in FSs compared to control group. There was increased in glucose, phosphorus levels and decrease in sodium, chloride levels. The results do not suggest that SCN1A p. Thr 1067 Ala or c.3184A/G (rs2298771) are susceptibility factors for febrile seizures and the fever plays an important role in causing disturbances in electrolyte balance.