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SCN8A Publications
Below is a list of SCN8A Publications related to SCN8A epilepsy.
On the Feasibility of Quantifying Sodium Channel NaV1.6 Protein in Mouse Brain using targeted UHPLC-ESI-MRM Mass Spectrometry.
2/6/2019 Article
We can obtain quantitative data of the expression of the sodium channel Nav 1.6 by choosing a certain protein sequence (DSLFPIR) and monitoring the amount of it being made by using multiple reaction monitoring (MRM), which measures concentrations of proteins in plasma. In the three types of mice studied, the wild type(+/+) and heterozygous mutant(D/+) had the same amount of expression, whereas the mutant null (+/-) had only 50% of this amount of expression of Nav 1.6.
"Breath holding spells" in a child with SCN8A-related epilepsy: Expanding the clinical spectrum
1/23/2019 Article
SCN8A has a spectrum of phenotypes, a case of a seizures with an unclear origin has expanded the spectrum. The 14-month-old girl was originally diagnosed with episodes of reflex-anoxic seizures (non-epileptic) and breath-holding spells after cessation of crying. The girl was discovered to have a de novo mutation in the SCN8A gene, and a video-EEG suggests she was experiencing generalized seizures. She now takes a mixture of phenobarbital, levetiracetam, and oxcarbazepine, where the addition of oxcarbazepine caused a drastic reduction in episodes then an open-ended seizure-free period.
Prominent role of forebrain excitatory neurons in SCN8A encephalopathy
1/2/2019 Article
The activation of the R1872W, an SCN8A mutation, by several different factors was tested on mice. EIIa-Cre and Nestin-Cre resulted in early onset seizures and death, Emx1-Cre lengthened the life span of the mouse, while Gad2-Cre and D1x5/6-Cre did not induce seizures. These test show that lifelong treatments will be required for successful therapy.
Common terms for rare epilepsies: Synonyms, associated terms, and links to structured vocabularies.
1/29/2018 Article
Due to missing codes in the International Classification of Diseases (ICD) system identification of rare epilepsy syndromes can be difficult. This group surveyed parent advocates, providers, and caregivers and found that emerging rare epilepsies, like SCN8A, were underrepresented. This illustrates the need for medical vocabularies to fill the gaps in representation of these rare epilepsies.
Differential roles of NaV1.2 and NaV1.6 in regulating neuronal excitability at febrile temperature and distinct contributions to febrile seizures.
1/25/2018 Article
The sodium channels Nav1.2 and Nav1.6 are vitally important for the control of febrile seizures. When Nav1.2 is knocked out it is perinatal lethal in mice. A Nav1.6 knockout leads to a higher susceptibility to febrile seizures and lowers the temperature needed to induce the seizure.
High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies
11/2/2017 Article
The cause of developmental and epileptic encephalopathies is unknown in a majority of cases. The authors performed whole-genome sequencing in 197 individuals and performed meta-analysis to document de novo mutations in certain candidate genes.
Sodium channel subtypes are differentially localized to pre- and post-synaptic sites in rat hippocampus.
11/1/2017 Article
While sodium channels are known to influence neuronal excitability, the exact role of each subtype is unclear. Johnson et al. investigated three main sodium channel subtypes (Nav 1.1, 1.2, and 1.6) and found selective pre- and postsynaptic expression of voltage-gated sodium channels in glutamatergic synapses.
A Novel Inherited Mutation of SCN8A in a Korean Family with Benign Familial Infantile Epilepsy Using Diagnostic Exome Sequencing
11/1/2017 Article
Diagnostic exome sequencing identified a novel inherited mutation (p.Gly1476Asp) in the SCN8A gene. The paper reports the case of an infant and father with this mutation who had early onset benign familial infantile epilepsy but no cognitive impairment.
Early-onset epileptic encephalopathy with de novo SCN8A mutation
10/28/2017 Article
In this case study, a de novo mutation was reported in an EOEE patient who died from SUDEP. The data found help strengthen the association between SCN8A and EOEE and urge the screening for this mutation for early prevention of SUDEP.
De novo variants in the alternative exon 5 of SCN8A cause epileptic encephalopathy
9/28/2017 Article
Exome sequence data from 54 epilepsy patients and their unaffected parents to help identify the molecular diagnoses that were not initially provided. In the 54 trios, two de novo missense variants in SCN8A in the alternative exon 5A. This helps expand the range of SCN8A variants in epileptic encephalopathy.
Characterization of the axon initial segment of mice substantia nigra dopaminergic neurons.
7/22/2017 Article
Action potentials initiate at the axon initial segment and influence action potential waveform, firing pattern, and rate. Motor function and behavior depend on the firing of substantia nigra pars compacta dopaminergic neurons, and so the axon initial segment of these neurons were characterized in the mouse. 1.6
Aberrant sodium channel currents and hyperexcitability of medial entorhinal cortex neurons in a mouse model of SCN8A encephalopathy
7/4/2017 Article
Effects of the N1768D mutation on the neurons within the medial entorhinal cortex (mEC) were studied in this paper. mEC neurons are known to provide excitatory input to the dentate gyrus and hippocampus and are known to elevate the circuit excitability in animal models with temporal lobe epilepsy. It was found that unlike hippocampal or neocortical neurons, the mEC neurons are hyperexcitable and this increase in excitability precedes the onset of seizures by more than one month.
Severe bone loss and multiple fractures in SCN8A-related epileptic encephalopathy
7/1/2017 Article
While it is unknown whether SCN8A mutations can lead to skeletal complications, there have been reports of children with SCN8A mutations who also suffer from skeletal fractures. Researchers analyzed skeletal phenotypes of 2-week-old SCN8A-null mice and revealed there was reduced bone mass as compared to control littermates.
Loss-of-function variants of SCN8A in intellectual disability without seizure
6/7/2017 Article
Two SCN8A missense mutations (p.Gly964Arg and p.Glu1218Lys) were examined in this paper that present with intellectual disability and developmental delay but no seizures. Both these mutations completely prevented the generation of sodium currents within transfected cell lines. These observations extend the established phenotypic spectrum of SCN8A.
Phenytoin as a last‐resort treatment in SCN8A encephalopathy
5/16/2017 Article
A case report of a 5-year old boy with an SCN8A mutation (p.Val233Ile) is presented here. Initial treatment of the boy consisted of valproic acid and phenobarbital which granted seizure freedom for 1 year. After this status epilepticus events occurred once every 2-3 months so phenobarbital was switched out and other drugs were used as part of the child's drug therapy. Ketogenic diet, levetiracetam, zonisamide, and topiramate therapy all led to rapid deterioration. Phenytoin was found to be a reasonable rescue medication, but as a maintenance drug was found to cause severe side effects.
Gene panel analysis for nonsyndromic cryptogenic neonatal/infantile epileptic encephalopathy
5/4/2017 Article
A cohort of 31 patients with severe infantile epileptic encephalopathy with seizure onset prior to 24 month was investigated in this paper. Next-generation sequencing was used for 430 epilepsy-associated genes to identify pathogenic variants in this cohort. One patient reported an SCN8A mutation (p.Arg1617Gln) with moderate intellectual disability and developmental regression.
Transient upregulation of Nav1.6 expression in the genu of corpus callosum following middle cerebral artery occlusion in the rats
4/20/2017 Article
The expression and distribution of Nav1.6 in rats in a stroke-like model was examined in this paper. The expression of Nav1.6 mRNA levels was decreased in these rats during the acute phase after reperfusion. Interestingly, the number of Nav1.6 positive cells was dramatically increased at 6 hours, and then decreased at 12 and 24 hours.
Advances in epilepsy gene discovery and implications for epilepsy diagnosis and treatment
4/1/2017 Article
This article outlines recent findings in a variety of genetic mutations related to epilepsy, including SCN8A. It summarizes how precision medicine and gene discovery are facilitating rapid progress in the classification of epilepsy, as well as development of medications targeted toward patients with these specific genetic mutations.
Neuronal hyperexcitability in a mouse model of SCN8A epileptic encephalopathy
2/13/2017 Article
Recent experimentation through mouse models suggests that a N1768D mutation in SCN8A results in hyperexcitability and an elevated persistent sodium current in hippocampal neurons. This data suggests that SCN8A plays a role in neural excitability, which could explain the mechanism through which early infantile epileptic encephalopathy (EIEE) causes severe seizures and cognitive impairment.
SCN8A mutation in a child presenting with seizures and developmental delays
11/1/2016 Article
Researchers identified a de novo missense SCN8A mutation (p.Leu267Ser, c.800T>C) in a 4 year old female. This case report provides information on the child's clinical presentation,family history, and genetic analysis.
Cardiac Arrhythmia in a Mouse Model of Sodium Channel SCN8A Epileptic Encephalopathy
10/26/2016 Article
De novo mutations in the SCN8A gene are at an increased risk for sudden unexpected death in epilepsy (SUDEP). In this study, the cardiac phenotype of a mouse model expressing the p.Asn1768Asp mutation in SCN8A was investigated for alterations in cardiac excitability. The authors observed prolongation of the early stages of action potential repolarization in mutated myocytes.
SCN8A-Related Epilepsy with Encephalopathy
8/25/2016 Article
A summary of the clinical characteristics of SCN8A-related epilepsy. This complete review covers everything from available testing and diagnostic procedures available for SCN8A-related epilepsy, to the management of symptoms, in order to serve as a point-of-care resource for clinicians.
Detection of Fetal Seizures Guides Approach to Diagnosis and Treatment
8/16/2016 Article
This paper describes the first reported case of a SCN8A mutation (p.Ile240Val) with clinical prenatal-onset seizures. Ultrasonography was found to be useful for identifying fetal seizures which may be treatable in utero. Finally the authors report that the clinical approach to fetal seizures should involve a multidisciplinary team.
The SCN8A Mutation p.ll1327Val Displays Elevated Sensibility to the Anticonvulsant Phenytoin
7/4/2016 Article
In a recent study it was shown that high doses of phenytoin were effective in four patients with SCN8A encephalopathy. Researchers have created a cell line with a SCN8A mutation (p.Ile1327Val) to study the cell's response to phenytoin.
Benign Infantile Seizures and Dyskinesia - An Unexpected Twist
12/22/2015 Article
SCN1A was initially discovered in GEFS+, an autosomal dominant familial epilepsy syndrome. SCN2A was first identified in Benign Familial Neonatal-Infantile Seizures (BFNIS), also representing an autosomal dominant familial epilepsy syndrome. SCN8A, the third epilepsy-related sodium channel gene, has only...
2015 - This is What You Need to Know About SCN8A
8/31/2015 Article
In 2015, SCN8A has emerged as an important gene in epileptic encephalopathy. SCN8A encodes the voltage-gated sodium channel alpha subunit Nav1.6, and was first implicated in epileptic encephalopathy in 2012. Since then, approximately 100 cases of early-infantile...
SCN8A Encephalopathy - How it differs from Dravet Syndrome
1/13/2015 Article
For some reason, SCN8A always met some resistance. In contrast to other epilepsy genes, it took a while for the community to embrace this gene as a genuine cause of epileptic encephalopathies. A recent publication in Neurology now investigates the phenotypic spectrum of SCN8A encephalopathy – and points out important features that distinguish this condition from Dravet Syndrome.