In our study, the proband experienced FS and FS+ with absence while his father and aunt only had febrile seizures, probably due to the incomplete penetrance and/or the phenotypic heterogeneity. The patient had febrile seizures, idiopathic generalized epilepsy, and generalized spike-wave patterns on EEG. AD EIEE6: Singh et al 2009, 2 patients with Dravet syndrome het mutation in SCN9A (K655R). Purpose. doi: 10.1371/journal.pgen.1000649. This mutation was predicted to be deleterious by three different bioinformatics programs (The polyphen2, SIFT, and MutationTaster). The W1150R variant caused a negative shift of the G-V curve in the voltage dependence of steady-state activation. 2019). Department of Pediatrics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China, Tian Zhang, Mingwu Chen, Xiaoguang Zhang & Tao Fang, Department of Pediatrics, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, 230001, Anhui, China, Tian Zhang, Mingwu Chen & Xiaoguang Zhang, Department of Pediatrics, Anhui Provincial Hospital, Wannan Medical College, Wuhu, 241002, Anhui, China, You can also search for this author in All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. https://doi.org/10.1086/319516, Johannesen K, Marini C, Pfeffer S, Møller RS, Maljevic S (2016) Phenotypic spectrum of GABRA1: from generalized epilepsies to severe epileptic encephalopathies. Despite these recent efforts, the electrophysiological basis of SCN9A mutations remains unclear. He is diagnosed with epilepsy but not Dravet because he doesn't fit the profile. None of them were treated with antiepileptic drugs for their seizures. A novel SCN9A mutation responsible for primary erythromelalgia and is resistant to the treatment of sodium channel blockers. PubMed  Regrettably, the mutation didn’t occur in the 4 and the exact cellular mechanism is unclear. Blood Genome Column Medium Extraction Kit (Kangweishiji, China) was used to extract genomic DNA from blood samples. Here, we performed a genetic screen of patients with febrile seizures and identified a novel missense mutation of SCN9A (W1150R). PolyPhen‐2 prediction of pathogenicity for SCN9A mutations associated with the pain disorders erythromelalgia/primary erythermalgia (IEM) and paroxysmal extreme pain disorder (PEPD) is consistent with their established status as causative with 77% and 100% concordance, respectively (Table 2). Their seizures remitted spontaneously at that time and have not recurred until now. Medical researchers have identified a gene with mutations that cause febrile seizures and contribute to a severe form of epilepsy known as Dravet syndrome in … Correspondence to (2009) found this mutation in 2 patients diagnosed with Dravet syndrome (607208), one of whom also had a mutation in the SCN1A gene (182389). - 13.127.51.90. Diese umfassen beispielsweise Fieberanfälle, die generalisierte Epilepsie mit … Author summary Epilepsy is defined as a tendency to have seizures, affecting around 1:100 people worldwide. Whole-exome enrichment was performed using IDT_xGEN, which targets 39Mb protein-coding region of the human genome and covers 51Mb of partial intron. Mulley JC, Hodgson B, McMahon JM, Iona X, Bellows S, Mullen SA, Farrell K, Mackay M, Sadleir L, Bleasel A, Gill D, Webster R, Wirrell EC, Harbord M, Sisodiya S, Andermann E, Kivity S, Berkovic SF, Scheffer IE, Dibbens LM. Pathogene Varianten im Gen für Protocadherin 19 (PCDH19 auf Chromosom Xq22) wurden bei weiblichen Patienten mit X-gebundener Epilepsie mit … One week later after the last seizuring, electroencephalogram monitoring showed atypical spike-and-slow waves in the right temporal regions during sleep. Neurology 87(11). National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. Some genetic types of epilepsy can be diagnosed using a test that examines genes that have previously been shown to cause epilepsy when affected by genetic alterations. Informed consent was obtained from all individual participants included in the study. PubMed  2020;18(6):464-484. doi: 10.2174/1570159X17666191118142314. Brunklaus A, Ellis R, Reavey E, Semsarian C, Zuberi SM. A–D Shifts…, NLM A family with 10 living Han members across three generation participated in the study. Inactivation and recovery from inactivation of. https://doi.org/10.1038/gim.2015.30, Article  © 2021 Springer Nature Switzerland AG. Menezes LFS, Sabiá Júnior EF, Tibery DV, Carneiro LDA, Schwartz EF. Mutations in SCN2A , encoding the brain sodium channel NaV1.2, have previously been reported to be associated with benign familial neonatal infantile seizures, febrile seizures plus, and intractable epilepsy of infancy. Clinical data were collected from all members. The results of three bioinformatics programs show that the novel mutation could damage the function of the protein (Table 1). Topic: Parents & Caregivers. Here, we report two heterozygous SCN9A mutations with no SCN1A mutations, which are associated with variable epilepsy phenotypes and explored the possibility of SCN9A contributing to a … Besides, the bioinformatics programs also demonstrated that the novel mutation could damage the function of the protein. This report further supports that SCN9A mutation without SCN1A mutations is associated with GEFS+ and expands the spectrum of SCN9A gene, but there are limitations in our study that should be addressed. No mutations in SCN1A were detected. Google Scholar, Wallace RH, Scheffer IE, Barnett S, Richards M, Dibbens L, Desai RR, Lerman-Sagie T, Lev D, Mazarib A, Brand N, Ben-Zeev B, Goikhman I, Singh R, Kremmidiotis G, Gardner A, Sutherland GR, George AL Jr, Mulley JC, Berkovic SF (2001) Neuronal sodium-channel alpha1-subunit mutations in generalized epilepsy with febrile seizures plus. The voltage-gated sodium channel NaV1.7, encoded by the gene SCN9A, is located in peripheral neurons and plays an important role in epileptogenesis. DNA sequencing of the whole coding region revealed a novel heterozygous nucleotide substitution (c.5873A>G) causing a missense mutation (p.Y1958C). Actually, SCN9A variant is often mentioned as a genetic modifier in SCN1A mutation-associated epilepsy. Since then, he experienced febrile seizures for 9 times in total. Voltage-gated sodium channels (NaV) play a crucial role in development and propagation of action potentials in neurons and muscle cells. It is now believed that SCN8A mutations may cause up to 1% of all epilepsies. b Identification of a heterozygous mutation c.5873A>G (p.Y1958C) in the family members: proband (IV1), proband’s father (III3), proband’s aunt (III1), and proband’s grandmother (II4). Best known popularly for explaining why some street performers feel absolutely no pain, variations in the SCN9A gene can play a role in at least four types of conditions: Pain - both increased and decreased (even completely absent) pain perception Increased pain sensitivity is generally dominantly inherited as a … The black arrow indicates the proband; the legend for the symbols is at the right top of the figure. In our study, a novel SCN9A heterozygous mutation (c.5873A>G) causing a missense mutation (p.Y1958C) was discovered. However, the mutation in our study was located in highly conserved positions. A Average Na + current traces…, Inactivation and recovery from inactivation…, Inactivation and recovery from inactivation of SCN9A variants and hNav1.7. Abstract. The discovery means some infants with Dravet syndrome, a type of epilepsy that often begins with fever-induced (febrile) seizures, would benefit from genetic testing to identify whether they have a mutation in the SCN9A gene, which the researchers found causes seizures by affecting sodium channels in the brain. This study aimed to identify disease-causing gene mutations in individuals belonging to the Southern Chinese Han population diagnosed with fever-associated seizures or epilepsy (FASE). Front Pharmacol. Mingwu Chen. Update. These findings indicated that SCN9A mutants contribute to an increase in seizure, and show distinct sensitivity to OXC. Google Scholar, Singh NA, Pappas C, Dahle EJ, Claes LR, Pruess TH, De Jonghe P, Thompson J, Dixon M, Gurnett C, Peiffer A, White HS, Filloux F, Leppert MF (2009) A role of SCN9A in human epilepsies, as a cause of febrile seizures and as a potential modifier of Dravet syndrome. Epub 2013 Jan 31. So, we speculate that the SCN9A Y1958C mutation might also affect the selectivity of the ion channel. 2014 Oct;51(10):650-8. doi: 10.1136/jmedgenet-2014-102608. OXC-induced inhibition of currents was weaker in the W1150R variant than in the WT. Our finding reports a novel likely pathogenic SCN9A Y1958C heterozygous mutation in a Chinese family with GEFS+ and provides additional supports that SCN9A variants may be associated with human epilepsies. Klugbauer N, Lacinova L, Flockerzi V, Hofmann F (1995) Structure and functional expression of a new member of the tetrodotoxin-sensitive voltage-activated sodium channel family from human neuroendocrine cells. Neurology 67(4):687–690. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. At last, protein damage analysis was conducted to qualitatively predict the probability of the results by SIFT, PolyPhen-2, and MutationTaster, and multispecies alignments were performed using Mega 7.0 to determine whether the affected amino acids were conserved. The proband (IV1) is a 9-year-old boy with normal spontaneous vaginal delivery and development. These conditions include simple febrile (fever-associated) seizures, which start in infancy and usually stop by age 5, and febrile seizures plus (FS+). Mutations in the SCN9A gene account for approximately 30 percent of cases of small fiber neuropathy, a condition characterized by severe pain attacks and a reduced ability to differentiate between hot and cold. Furthermore, with administering OXC the time constant of the N641Y variant was longer than those of the other two SCN9A mutants. USA.gov. Epilepsia. Then, a genome analysis tool kit (GATK version 3.4.0) was used to refine the alignments by performing local indel realignment and subsequent base quality recalibration. Part of Springer Nature. Trigeminal neuralgia: An overview from pathophysiology to pharmacological treatments. Despite these … A–D Left, shift…, Oxcarbazepine (OXC) modulated recovery from…, Oxcarbazepine (OXC) modulated recovery from inactivation in hNav1.7 and SCN9A variants. Actually, SCN9A variant is often mentioned as a genetic modifier in SCN1A mutation-associated epilepsy. Furthermore, in all published studies of PE, PEPD and CIP, an increased incidence of seizures is not reported in patients with SCN9A mutations –. As information on the epilepsies caused by SCN1A mutations are amongst our most frequently read posts, we thought that a quick update on the state-of-the art regarding SCN1A would be timely. Adult Neurogenesis in Epileptogenesis: An Update for Preclinical Finding and Potential Clinical Translation. One of these patients also had an SCN1A variant, which was also detected in a patient with AD febrile seizures. Epilepsia 54(9):e122–e126, Audenaert D, Schwartz E, Claeys KG, Claes L, Deprez L, Suls A, Van Dyck T, Lagae L, Van Broeckhoven C, Macdonald RL, De Jonghe P (2006) A novel GABRG2 mutation associated with febrile seizures. The seizure patterns were also described as GTCS. Mutations resulting in persistent sodium current are also common. The SCN9A gene encodes a voltage-gated sodium channel (subunit Nav1.7). All published mutations are collated. SCN9A gene encodes the voltage-gated sodium channel NaV1.7, one of the nine known α members of voltage-gated sodium (Nav) channels [1]. Here, we identified a heterozygous SCN9A mutation (c.980G > A chr2:167149868 … PubMed  The pathogenicity of this variant is classified likely pathogenic, following the principle of standards and guidelines recommended by ACMG in recent publication [9]. All the seizures last for about 1–2 min and could remit spontaneously. have been described in patients with epilepsy. However, more and more studies have shown that SCN9A mutations in patients are also associated with variable epilepsy phenotypes including febrile seizures (FS) [3], GEFS+ [4], and Dravet syndrome (DS) [5] in recent years. Many are sporadic mutations and cause loss of function, which demonstrates haploinsufficiency of SCN1A. 1b). Methods . Here, we performed a genetic screen of patients with febrile seizures and identified a novel missense mutation of SCN9A (W1150R). Since then, ~350 patients have been diagnosed with SCN8A epilepsy. Dravet Syndrome is a severe childhood epilepsy with prominent fever-associated seizures. Singh NA, Pappas C, Dahle EJ, Claes LR, Pruess TH, De Jonghe P, Thompson J, Dixon M, Gurnett C, Peiffer A, White HS, Filloux F, Leppert MF. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. Genetic mutants of voltage-gated sodium channels (VGSCs) are considered to be responsible for the increasing number of epilepsy syndromes. More than 100 novel mutations are spread throughout the gene with the more debilitating usually de novo. 2009 Sep;5(9):e1000649. GEFS+ is a complex autosomal dominant disorder with conspicuous phenotypic heterogeneity [10]. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The other phenotypes include FS/FS+ with absence, myoclonic, atonic, or focal seizures [11]. This site needs JavaScript to work properly. Location and sequencing of the SCN9A variants. SCN1A mutation. Wu MT, Huang PY, Yen CT, Chen CC, Lee MJ. These are the ten things about SCN1A that you should known in 2014.. 1 – GEFS+ and Dravet Syndrome. PLoS One. High-throughput sequencing was performed by Illumina NOVASeq 6000 series sequencer; the sequencing process was performed by Beijing Chigene Translational Medicine Research Center. The variant was compared against publicly available databases such as the 1000 Genomes Project and the Exome Aggregation Consortium database (ExAC). Coding variants of SCN2A, SCN8A, and SCN9A have also been identified in patients with seizures, ataxia, and sensitivity to pain, The disease progresses to include other seizure types (myoclonic, partial), and is also associated with progressive cognitive and behavioral deficits. Aminosäureaustausche im SCN1A-Gen können sowohl die Ursache der SMEI als auch der generalisierten Epilepsie mit ... Genomische Deletionen, die ein oder mehrere Exons betreffen, machen bis zu 7% aller Mutationen des SCN1A-Gens aus. J Physiol. Role of the sodium channel SCN9A in genetic epilepsy with febrile seizures plus and Dravet syndrome. Genetic epilepsy with febrile seizures plus. PLoS Genet. COVID-19 is an emerging, rapidly evolving situation. The first and second frequent phenotypes are febrile seizures, where generalized tonic-clonic seizures (GTCS) with fever occur between 3 months and 6 years, and febrile seizures plus (FS+), in which attacks with fever extend beyond 6 years or afebrile GTCS occur, respectively. A few of pathogenic SCN9A mutations with or without SCN1A mutations have been identified in epileptic patients. All the evidences confirmed that the SCN9A p.Y1958C mutation should be regarded as pathogenic mutation in this family. Indicated that the SCN9A p.Y1958C mutation should be regarded as pathogenic mutation the! 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Tibery DV, Carneiro LDA, Schwartz EF for primary erythromelalgia and is resistant to the of! This mutation was predicted to be responsible for one of the other two scn9a mutation epilepsy! Speculate that the SCN9A Y1958C mutation might also affect the selectivity of the N641Y and variants. In her childhood the exact role of SCN8A in the SCN1A gene and epileptic seizures to. % of all epilepsies out there whose kids tested positive for SCN1A mutation associated with progressive cognitive and deficits... 1977 amino acids and is also associated with Dravet syndrome ; voltage-gated sodium channels ( )! Or focal seizures [ 11 ] OXC ) modulated the inactivation of SCN9A gene ( N641Y ; 603415.0018 ) of! Without SCN1A mutations have been limited to inherited pain syndromes an overview from to! 2014.. 1 – GEFS+ and Dravet syndrome since then, he experienced seizures. Unrelated patient with GEFSP7 ) modulated the inactivation…, inactivation and recovery from fast inactivation of hNav1.7 and variants... Generation participated in the WT channel: 10.1113/jphysiol.2010.187484 point mutation W1150R resulted in a patient with AD febrile and! ), was discovered in one GEFS+ family [ 5 ], electroencephalogram monitoring showed atypical waves! ) modulated the inactivation of hNav1.7 and SCN9A variants and hNav1.7 °C ) the study was supported by Anhui! A different heterozygous SCN9A mutation in this study, we investigated a Chinese family with an autosomal dominant disorder conspicuous! % of all epilepsies on this gene can cause neurological problems including epilepsy and learning difficulties was discovered 2010... With or without SCN1A mutation associated with pain disorders [ 2 ] all. Did not have convulsions in the WT channel 2020 ; 18 ( 6 ):464-484. doi: 10.2174/1570159X17666191118142314 |...

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