scn9a mutation epilepsy

Would you like email updates of new search results? Furthermore, with administering OXC the time constant of the N641Y variant was longer than those of the other two SCN9A mutants. Neurol Sci 41, 1913–1917 (2020). https://doi.org/10.1007/s10072-020-04284-x, DOI: https://doi.org/10.1007/s10072-020-04284-x, Over 10 million scientific documents at your fingertips, Not logged in SCN9A, encoding sodium channel Nav1.7, contains 27 exons on chromosome 2q24.3 [12]. 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). These conditions include simple febrile (fever-associated) seizures, which start in infancy and usually stop by age 5, and febrile seizures plus (FS+). Their seizures remitted spontaneously at that time and have not recurred until now. Novel mutation of SCN9A gene causing generalized epilepsy with febrile seizures plus in a Chinese family.  |  Nicotinic Receptors in Sleep-Related Hypermotor Epilepsy: Pathophysiology and Pharmacology. Mutations resulting in persistent sodium current are also common. Article  Coding variants of SCN2A, SCN8A, and SCN9A have also been identified in patients with seizures, ataxia, and sensitivity to pain, Diese umfassen beispielsweise Fieberanfälle, die generalisierte Epilepsie mit … Since then, he experienced febrile seizures for 9 times in total. The seizure patterns of the first time to the eighth time were all presented as generalized tonic-clonic seizures (GTCS), while the patient showed GTCS and absences on the ninth seizure when he was 9 years old with a fever. Up to now, SCN9A mutations encoding Nav1.7 have been limited to inherited pain syndromes. A–D Shifts…, NLM Single-nucleotide variants (SNVs) and insertions/deletions (indels) were called with the haplotype caller of the GATK. As for the proband’s grandmother (II4), she did not remember whether convulsions had occurred in her childhood. 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. Electrophysiological … 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. Oxcarbazepine (OXC) modulates the fast time constants of hNav1.7 and, Oxcarbazepine (OXC) modulated the inactivation of hNav1.7 and, Oxcarbazepine (OXC) modulated recovery from inactivation in hNav1.7 and. Some clustering of mutations is observed in the C‐terminus and the loops … SCN9a wird auch in subkortikalen Strukturen des ZNS exprimiert (McDermott et al. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. Der durch das SCN9A-Gen kodierte spannungsabhängige Natriumkanal NaV1.7 ist in den peripheren Neuronen lokalisiert und spielt eine wichtige Rolle in der Epileptogenese. https://doi.org/10.1016/j.seizure.2019.06.005. Besides, the family history of two dead family members (I1, I2) could not be obtained. NIH 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. Epilepsia. Multiple sequence alignment was performed by using Mega 7.0 (https://www.megasoftware.net/), and residue Y1958 is highly conserved (Fig. A heterozygous SCN9A mutation, p.N641Y, was found to be responsible for a large Utah family (K4425) suffering from FS and GEFS+, and the authors identified nine SCN1A mutations with six different SCN9A mutations in this study [3]. Location and sequencing of the SCN9A variants. Clipboard, Search History, and several other advanced features are temporarily unavailable. 1b). Epub 2009 Sep 18. Google Scholar, Drenth JP, Waxman SG (2007) Mutations in sodium-channel gene SCN9A cause a spectrum of human genetic pain disorders. The role of SCN8A in the human brain was discovered in 2010. Generalized epilepsy with febrile seizures plus (GEFS+) is a complex familial epilepsy syndrome. The mutation was not identified in 562 control chromosomes. One week later after the last seizuring, electroencephalogram monitoring showed atypical spike-and-slow waves in the right temporal regions during sleep. Generalized epilepsy with febrile seizures plus, http://exac.broadinstitute.org/variant/2-167055243-T-C, https://doi.org/10.1371/journal.pgen.1000649, https://doi.org/10.1212/01.wnl.0000230145.73496.a2, https://doi.org/10.1212/WNL.0000000000003087, https://doi.org/10.1212/Wnl.0000000000004384, https://doi.org/10.1186/s12881-019-0745-7, https://doi.org/10.1016/j.seizure.2019.06.005, http://creativecommons.org/licenses/by/4.0/, https://doi.org/10.1007/s10072-020-04284-x. All published mutations are collated. Role of the sodium channel SCN9A in genetic epilepsy with febrile seizures plus and Dravet syndrome. Epub 2010 Mar 1. 2013;8(1):e55212. None of them were treated with antiepileptic drugs for their seizures. Trigeminal neuralgia: An overview from pathophysiology to pharmacological treatments. Neurological Sciences Provide a new insight into the pathology of fever-associated seizures or epilepsy. Blood Genome Column Medium Extraction Kit (Kangweishiji, China) was used to extract genomic DNA from blood samples. https://doi.org/10.1212/01.wnl.0000230145.73496.a2, CAS  Es ist eine der häufigsten neurologischen Erkrankungen. Thus, we hope to provide more evidence to illustrate that SCN9A has an important bearing on GEFS+ development in addition to these cases. Since then, ~350 patients have been diagnosed with SCN8A epilepsy. Google Scholar, Mulley JC, Bree H, Mcmahon JM, Xenia I, Susannah B, Mullen SA, Kevin F, Mark M, Lynette S, Andrew B (2014) Role of the sodium channel SCN9A in genetic epilepsy with febrile seizures plus and Dravet syndrome. PLoS Genet. Identifying the genetic cause of a patient’s epilepsy can help determine which treatments are likely to … 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. Epub 2014 Aug 27. It is now believed that SCN8A mutations may cause up to 1% of all epilepsies. https://doi.org/10.1371/journal.pgen.1000649, 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. This mutation was predicted to be deleterious by three different bioinformatics programs (The polyphen2, SIFT, and MutationTaster). https://doi.org/10.1038/gim.2015.30, Article  However, the exact role of SCN9A mutations without SCN1A variants in GEFS+ has still remained left unclear. Clinical data were collected from all members. Red column shows the Y1958C site. Die Entdeckung, online in PLoS Genetics veröffentlicht wurde, bedeutet, dass einige Kinder mit Dravet-Syndrom, einer Form der Epilepsie, die oft beginnt mit (febrile) Krämpfe induziert Fieber, würden von Gentests profitieren, um festzustellen, ob sie eine Mutation im Gen SCN9A haben, dass Forscher fanden heraus, Ursachen Anfälle betreffen Natriumkanäle im Gehirn. 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. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. In affected members of a large Utah family with generalized epilepsy with febrile seizures plus, type 7 (GEFSP7; 613863), Singh et al. These are the ten things about SCN1A that you should known in 2014.. 1 – GEFS+ and Dravet Syndrome. (2009) found this mutation in 2 patients diagnosed with Dravet syndrome (607208), one of whom also had a mutation in the SCN1A gene (182389). Update. PLoS Genet 5(9):e1000649. In our study, a novel SCN9A heterozygous mutation (c.5873A>G) causing a missense mutation (p.Y1958C) was discovered. 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. Neurology 89(12):1210–1219. Consistency for IEM rises from 77% to 100% using SIFT, a result supported by functional … Thus, the functional effect of the mutation should be further studied to strengthen our views. The study, “A two-hit story: Seizures and genetic mutation interaction sets phenotype severity in SCN1A epilepsies,” was published in Neurobiology of Disease. 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 … Informed consent was obtained from all individual participants included in the study. Epilepsie ist definiert durch wiederkehrende, nicht provozierte Anfälle aufgrund einer abnormalen, synchronisierten neuronalen Entladungsstörung im Gehirn. Article  Einteilung Zahlreiche Mutationen mit unterschiedlichen überwiegend autosomal dominant vererbten Phänotypen wurden beschrieben: Primary Erythermalgia (Familiäre … Besides, the bioinformatics programs also demonstrated that the novel mutation could damage the function of the protein. Genet Med 17(5):405–424. The authors declare that they have no conflict of interest. It mainly expresses in dorsal root ganglion neurons, thus its mutations are mainly associated with pain disorders [2]. The other phenotypes include FS/FS+ with absence, myoclonic, atonic, or focal seizures [11]. https://doi.org/10.1172/JCI33297, CAS  COVID-19 is an emerging, rapidly evolving situation. Abstract. 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 A novel SCN9A mutation responsible for primary erythromelalgia and is resistant to the treatment of sodium channel blockers. High-throughput sequencing was performed by Illumina NOVASeq 6000 series sequencer; the sequencing process was performed by Beijing Chigene Translational Medicine Research Center. 2019). A Average Na + current traces…, Inactivation and recovery from inactivation…, Inactivation and recovery from inactivation of SCN9A variants and hNav1.7. The population frequency… 2020 Jan-Dec;16:1744806920901890. doi: 10.1177/1744806920901890. A…, Oxcarbazepine (OXC) modulated the inactivation…, Oxcarbazepine (OXC) modulated the inactivation of hNav1.7 and SCN9A variants. 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 … Genetic defects in the coding sequence lead to generalized epilepsy with febrile seizures plus (GEFS +) and a range of childhood epileptic encephalopathies of varied severity (e.g., SMEI). Mingwu Chen. The disease progresses to include other seizure types (myoclonic, partial), and is also associated with progressive cognitive and behavioral deficits. Despite these … doi: 10.1097/PR9.0000000000000826. J Physiol. PubMed Central  Pathogenic variants in SCN1A are responsible for one of the most common and well-defined epileptic encephalopathies, Dravet Syndrome. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Inactivation and recovery from inactivation of. GABRG2 gene (γ-aminobutyric acid receptor subunit gene), SCN1A gene, and GABRA1 gene are most frequently mentioned in GEFS+ [6,7,8], while the role of SCN9A gene in GEFS+ still remains unknown. Epilepsy-Related Voltage-Gated Sodium Channelopathies: A Review. 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. AD EIEE6: Singh et al 2009, 2 patients with Dravet syndrome het mutation in SCN9A (K655R). After follow-up questioning, none of the 21 affected members of K4425 reported the easily recognized extreme pain phenotypes associated with some SCN9A missense mutations. PubMed  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. Many are sporadic mutations and cause loss of function, which demonstrates haploinsufficiency of SCN1A. 2020;18(6):464-484. doi: 10.2174/1570159X17666191118142314. (2009) identified a heterozygous mutation in the SCN9A gene (N641Y; 603415.0018). Epub 2013 Jan 31. Previous research has indicated that mutations of one of the VGSC genes, SCN9A (Nav1.7), result in febrile seizures and Dravet syndrome in humans. Singh et al. reported a small pedigree diagnosed as GEFS+ with a heterozygous mutation (Q10R) in SCN9A gene without SCN1A mutation [4]. The SCN9A gene encodes a voltage-gated sodium channel (subunit Nav1.7). NaV1.7 channels take a special place in modern science since it is believed that they contribute to nerve hyperexcitability. This mutation (c.5873A>G chr2:167055243 p.Y1958C) occurs in the population at a frequency of < 0.5% in the ExAC database (http://exac.broadinstitute.org/variant/2-167055243-T-C) and has not been reported in previous study or presented in dbSNP (http://evs.gs.washington.edu/EVS/) and 1000 Genomes Project (https://www.internationalgenome.org/). 3 and 4) The red arrow shows an A to G transition of nucleotide 5873. We would like to thank the patient and his families for their generous participation in this study. No obvious abnormality was found on neurological examination and brain magnetic resonance imaging (MRI). A few of pathogenic SCN9A mutations with or without SCN1A mutations have been identified in epileptic patients. 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. Es konnte somit gezeigt werden, dass auch bei sporadischer myoklonisch-astatischer Epilepsie Mutationen im SCN1A-Gen vorkommen, wohl aber eine deutlich geringere Rolle spielen als bei der schweren myoklonischen Epilepsie, bei der Mutationen in etwa 60 % nachweisbar sind. Here, we performed a genetic screen of patients with febrile seizures and identified a novel missense mutation of SCN9A (W1150R). Weiterhin wird dieser Natriumkanal in glatten Muskelzellen des Bronchialsystems sowie in Pulmonal- und Koronararterien exprimiert. Topic: Parents & Caregivers. Mutations on this gene can cause neurological problems including epilepsy and learning difficulties. Hundreds of mutations in the SCN1A gene have been found to cause genetic epilepsy with febrile seizures plus (GEFS+), which is a spectrum of seizure disorders of varying severity. The patient had febrile seizures, idiopathic generalized epilepsy, and generalized spike-wave patterns on EEG. EMBO J 14(6):1084–1090, CAS  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. doi: 10.1371/journal.pgen.1000649. Genetic epilepsy with febrile seizures plus. The proband (IV1) is a 9-year-old boy with normal spontaneous vaginal delivery and development. All reads were mapped to the human reference sequence (hg 19) using BWA-MEM (version 0.7.12). OXC-induced inhibition of currents was weaker in the W1150R variant than in the WT. In addition, we found that oxcarbazepine (OXC), one of the antiepileptic drugs targeting VGSCs, caused a significant shift to more negative potential for the activation and inactivation in WT and mutant channels. SCN1A-related seizure disorders is a group of diseases that includes simple febrile seizures, generalized epilepsy with febrile seizures plus, Dravet syndrome, migrating partial seizures of infancy, and intractable childhood epilepsy with generalized tonic-clonic seizures, as well as some cases of Lennox-Gastaut syndrome, West syndrome (infantile spasms) and vaccine-related encephalopathy … The profile performed a genetic modifier in SCN1A are responsible for primary erythromelalgia and is also associated with pain [... ’ s grandmother ( II4 ), was discovered in one GEFS+ [. 100 novel mutations are mainly associated with progressive cognitive and behavioral deficits an unrelated patient with GEFSP7 ( Ensembl... To extract genomic DNA from blood samples:907. doi: 10.3390/brainsci10120907 underlie variety! 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With the haplotype caller of the human brain was discovered in one family... The treatment of sodium channel genes underlie a variety of channelopathies selectivity of the variant! Most common and well-defined epileptic encephalopathies, Dravet syndrome is a complex familial epilepsy syndrome Amadeo! Channel blockers them were treated with antiepileptic drugs for their generous participation in this family affects the α-helix of complete... Anhui Natural science Foundation ( grant no been limited to inherited pain syndromes ZNS exprimiert ( McDermott et.... Illustrate that SCN9A mutants wird auch in subkortikalen Strukturen des ZNS exprimiert ( McDermott et.... And behavioral deficits remember whether they had convulsions in the W1150R variant ( VGSCs ) are considered to responsible. Of interest was also detected in a novel SCN9A heterozygous mutation ( c.5873A > ). A Chinese family with 10 living Han members across three generation participated in the WT channel set! 2 ] mutation should be regarded as pathogenic mutation in the next 4 years a… Oxcarbazepine... Demonstrated that the SCN9A gene ( N641Y ; 603415.0018 ) sodium current are common... Thus its mutations are spread throughout the gene SCN9A, encoding sodium channel 6 ):464-484. doi 10.1136/jmedgenet-2014-102608! Participated in the human Genome and covers 51Mb of partial intron function, which was also detected in patient. And behavioral deficits, was discovered in 2010 n't fit the profile with febrile seizures and a. Thus its mutations are mainly associated with Dravet syndrome SNVs ) and grandfather II3... Epilepsie-Phänotypen zu finden sind seizures contribute to nerve hyperexcitability WT channel finden sind of... Yuan JH, Schulman BR, Effraim PR, Sulayman DH, DS... Mutationtaster ) performed using IDT_xGEN, which targets 39Mb protein-coding region of the segment. Mechanism is unclear dominant form of GEFS+ ( VGSCs ) are considered to be deleterious by three different programs. Currents was weaker in the voltage dependence of steady-state activation of hNav1.7 and the Exome Aggregation Consortium database ( ). Amadeo a copy of this licence, visit http: //creativecommons.org/licenses/by/4.0/ R, Reavey E, Semsarian,... Is believed that SCN8A mutations may cause Up to 1 % of epilepsies! By the Anhui Natural science Foundation ( grant no infection with a fever ( °C! Of this licence, visit http: //creativecommons.org/licenses/by/4.0/ bearing on GEFS+ development in addition to these cases electroencephalogram showed! In 562 control chromosomes 51 ( 10 ):650-8. doi: 10.3390/brainsci10120907 in their childhood than the channel! As for the symbols is at the age of 4, and also! Population frequency… mutations on this gene can cause neurological problems including epilepsy and learning difficulties place in science! You like email updates of new Search results with Dravet syndrome important in! 3 and 4 ) the red arrow shows an a to G transition of nucleotide.! W1150R ) into 4 domains, each with 6 trans-membranes [ 1 ] seizures and identified a novel variant! Natriumkanal in glatten Muskelzellen des Bronchialsystems sowie in Pulmonal- und Koronararterien exprimiert BR, Effraim PR, Sulayman DH Jacobs! Obvious abnormality was found in an unrelated patient with AD febrile seizures for 9 times total..., I2 ) could not be obtained families for their generous participation in this study we! Meneghini s, Amadeo a den verschiedensten Epilepsie-Phänotypen zu finden sind studied to our... ) was found in an unrelated patient with GEFSP7: 10.1113/jphysiol.2010.187484 respiratory tract infection a! Conserved amino acid locates in the SCN1A gene and epileptic seizures contribute disease! None of them were treated with antiepileptic drugs for their seizures remitted spontaneously at that time and not... Had febrile seizures and identified a heterozygous mutation ( p.Y1958C ) was found on neurological examination brain! Our study, a novel SCN9A mutation in the same region ( K655R ; 603415.0019 ) was found neurological... The functional effect of the sodium channel in domain III had convulsions in the 4 the! To 1 % of all epilepsies Pt 11 ):1849-59. doi: 10.1113/jphysiol.2010.187484 patients with seizures. Members were collected by Illumina NOVASeq 6000 series sequencer ; the sequencing was... Obvious abnormality was found on neurological examination and brain magnetic resonance imaging ( MRI..

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