EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Common variants in the sodium channel gene, SCN1A, are associated with febrile seizures, and rare pathogenic variants in SCN1A cause the severe developmental and epileptic encephalopathy Dravet syndrome.
|
31755124 |
2020 |
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
|
0.100 |
Biomarker
|
disease |
BEFREE |
We hypothesized that over-expression of NaVβ1 would facilitate the function of residual voltage-gated channels and improve the DS phenotype in the Scn1a+/- mouse model of DS.
|
31830809 |
2020 |
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Two autopsy cases of sudden unexpected death from Dravet syndrome with novel de novo SCN1A variants.
|
31677916 |
2020 |
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
|
0.100 |
Biomarker
|
disease |
BEFREE |
To test the therapeutic potential of this approach, we delivered the Scn1a-dCas9 activation system to DS pups using adeno-associated viruses.
|
31607539 |
2020 |
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
This study also represents the first genetic analysis of the SCN1A gene in a Hungarian cohort with the DS and GEFS + syndrome phenotype.
|
31765958 |
2020 |
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Dravet syndrome (DS) is an early onset refractory epilepsy typically caused by de novo heterozygous variants in SCN1A encoding the α-subunit of the neuronal sodium channel Na<sub>v</sub>1.1.
|
31445158 |
2019 |
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Mice with heterozygous deletion of Scn1a (Scn1a<sup>+/-</sup>) model many features of Dravet syndrome, including spontaneous seizures and premature lethality.
|
30347190 |
2019 |
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
We test the hypothesis that the deletion of Scn1a in DS mice is associated with impaired circadian regulation of sleep.
|
31346614 |
2019 |
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Dravet syndrome (DS) is a genetic form of severe epilepsy often associated with mutation of the SCN1A gene encoding the voltage gated sodium channel Nav1.1.
|
31445030 |
2019 |
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Here we describe that a C57BL/6 J knock-in mouse strain carrying a heterozygous, clinically relevant SCN1A mutation (A1783V) presents a full spectrum of DS manifestations.
|
31578435 |
2019 |
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
De novo loss-of-function mutations in SCN1A are the main cause of Dravet syndrome, a catastrophic encephalopathy characterized by recurrent early-life febrile seizures, a number of other afebrile seizure types that are often refractory to treatment, and behavioral abnormalities including social deficits, motor dysfunction, and cognitive impairment.
|
31402621 |
2019 |
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
|
0.100 |
Biomarker
|
disease |
BEFREE |
Differentiating between Dravet syndrome and non-Dravet SCN1A-related phenotypes is important for prognosis regarding epilepsy severity, cognitive development, and comorbidities.
|
30527252 |
2019 |
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
|
0.100 |
Biomarker
|
disease |
BEFREE |
The induction of short repeated seizures, at the age of disease onset for Scn1a mouse models (P21), had no effect in WT mice, but transformed the mild/asymptomatic phenotype of Scn1a<sup>RH/+</sup> mice into a severe DS-like phenotype, including frequent spontaneous seizures and cognitive/behavioral deficits.
|
30659983 |
2019 |
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Identification of a precise genetic etiology can direct physicians to (i) prescribe treatments that correct specific metabolic defects (e.g., the ketogenic diet for GLUT1 deficiency, or pyridoxine for pyridoxine-dependent epilepsies); (ii) avoid antiepileptic drugs (AEDs) that can aggravate the pathogenic defect (e.g., sodium channel blocking drugs in SCN1A-related Dravet syndrome), or (iii) select AEDs that counteract the functional disturbance caused by the gene mutation (e.g., sodium channel blockers for epilepsies due to gain-of-function SCN8A mutations).
|
30870728 |
2019 |
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
|
0.100 |
Biomarker
|
disease |
BEFREE |
We propose that delayed maturation of GABAergic signaling may contribute to epileptogenesis in SCN1B- and SCN1A-linked DS.
|
30996233 |
2019 |
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Stiripentol, known to increase GABA<sub>A</sub> receptor activity as well as the metabolites of GABA<sub>A</sub> receptor agonists, is often used in the treatment of an epileptic encephalopathy, Dravet syndrome (DS), which is caused by mutations mainly in SCN1A and in other genes such as GABRG2.
|
31022638 |
2019 |
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
|
0.100 |
Biomarker
|
disease |
BEFREE |
In a mouse model of DS with a loss of function in Scn1a, reticular thalamic cells exhibited abnormally long bursts of firing caused by the downregulation of calcium-activated potassium SK channels.
|
30605686 |
2019 |
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
|
0.100 |
Biomarker
|
disease |
BEFREE |
These findings demonstrate that electrophysiological data from mammalian expression systems can serve as useful disease biomarker when evaluating SCN1A variants, particularly in view of new and emerging treatment options in DS.
|
31782251 |
2019 |
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Generation of three human induced pluripotent stem cell (iPSC) lines from three patients with Dravet syndrome carrying distinct SCN1A gene mutations.
|
31400703 |
2019 |
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Of over 700 SCN1A mutations known to cause Dravet syndrome, M72dup is the first to be identified in the NH<sub>2</sub>-terminus of Na<sub>V</sub>1.1.
|
31533007 |
2019 |
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
We observe elements of this interictal behavioral syndrome in seizure-prone DBA/2J mice and in mice with a pathogenic Scn1a mutation (modeling Dravet syndrome).
|
31697745 |
2019 |
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Targeted next-generation sequencing (NGS) was performed for 120 patients with unexplained epilepsy, including 71 patients with early-onset epileptic encephalopathies, and 16 patients with Dravet syndrome (including three patients with a Dravet-like phenotype) but without SCN1A pathogenic variants.
|
30776697 |
2019 |
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
|
0.100 |
Biomarker
|
disease |
BEFREE |
Patients with this variant show a well-defined genotype-phenotype correlation and present with developmental and early infantile epileptic encephalopathy that is far more severe than typical SCN1A Dravet syndrome.
|
30779207 |
2019 |
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
SCN1A mutations are associated with a spectrum of seizure-related disorders, ranging from a relatively mild form of febrile seizures to a more severe epileptic encephalopathy known as Dravet syndrome.
|
31009440 |
2019 |
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Dravet syndrome (DS) is a disease that is primarily caused by the inactivation of the SCN1A-encoded voltage-gated sodium channel alpha subunit (Nav1.1).
|
30529264 |
2019 |