نتایج جستجو برای: scn1a mutations

تعداد نتایج: 173129  

2015
Matthew T. Dinday Scott C. Baraban

Mutations in a voltage-gated sodium channel (SCN1A) result in Dravet Syndrome (DS), a catastrophic childhood epilepsy. Zebrafish with a mutation in scn1Lab recapitulate salient phenotypes associated with DS, including seizures, early fatality, and resistance to antiepileptic drugs. To discover new drug candidates for the treatment of DS, we screened a chemical library of ∼1000 compounds and ide...

2017
William M. Stern Josemir W. Sander John C. Rothwell Sanjay M. Sisodiya

OBJECTIVE Dravet syndrome is a rare neurodevelopmental disorder characterized by seizures and other neurologic problems. SCN1A mutations account for ∼80% of cases. Animal studies have implicated mutation-related dysregulated cortical inhibitory networks in its pathophysiology. We investigated such networks in people with the condition. METHODS Transcranial magnetic stimulation using single an...

2016
Sameer Al-Mehmadi Miranda Splitt Venkateswaran Ramesh Suzanne DeBrosse Kimberly Dessoffy Fan Xia Yaping Yang Jill A. Rosenfeld Patrick Cossette Jacques L. Michaud Fadi F. Hamdan Philippe M. Campeau Berge A. Minassian

Voltage-gated sodium channels (Navs) are mainstays of neuronal function, and mutations in the genes encoding CNS Navs (Nav1.1 [SCN1A], Nav1.2 [SCN2A], Nav1.3 [SCN3A], and Nav1.6 [SCN8A]) are causes of some of the most common and severe genetic epilepsies and epileptic encephalopathies (EE).1 Fibroblast-growth-factor homologous factors (FHFs) compose a family of 4 proteins that interact with the...

2016
Yishan Sun Sergiu P Paşca Thomas Portmann Carleton Goold Kathleen A Worringer Wendy Guan Karen C Chan Hui Gai Daniel Vogt Ying-Jiun J Chen Rong Mao Karrie Chan John Lr Rubenstein Daniel V Madison Joachim Hallmayer Wendy M Froehlich-Santino Jonathan A Bernstein Ricardo E Dolmetsch

Dravet Syndrome is an intractable form of childhood epilepsy associated with deleterious mutations in SCN1A, the gene encoding neuronal sodium channel Nav1.1. Earlier studies using human induced pluripotent stem cells (iPSCs) have produced mixed results regarding the importance of Nav1.1 in human inhibitory versus excitatory neurons. We studied a Nav1.1 mutation (p.S1328P) identified in a pair ...

Journal: :Experimental neurology 2013
Charles A Williams Agatino Battaglia

Multifactorial inheritance is the most important model accounting for the genetic behavior of the common epilepsies. Important to this model is the concept that many cumulative or synergistic risk genes ultimately lead to a threshold effect. Sophisticated molecular testing indicates that the common epilepsies are very polygenic without evidence of any single gene having even a mild-to-modest ri...

Journal: :Nature communications 2013
Scott C Baraban Matthew T Dinday Gabriela A Hortopan

Dravet syndrome is a catastrophic pediatric epilepsy with severe intellectual disability, impaired social development and persistent drug-resistant seizures. One of its primary monogenic causes are mutations in Nav1.1 (SCN1A), a voltage-gated sodium channel. Here we characterize zebrafish Nav1.1 (scn1Lab) mutants originally identified in a chemical mutagenesis screen. Mutants exhibit spontaneou...

Journal: :Neurology 2009
John J Millichap Sookyong Koh Linda C Laux Douglas R Nordli

Dravet syndrome (DS), previously known as severe myoclonic epilepsy in infancy (SMEI), is an epileptic encephalopathy that presents with prolonged seizures in the first year of life. The seizures often occur with fever or illness, and are frequently initially categorized as febrile seizures. The correct diagnosis of DS and appropriate follow-up are typically delayed. The EEG is normal at onset,...

Journal: :Molecular syndromology 2010
P Martin B Rautenstrauβ A Abicht J Fahrbach S Koster

Dravet syndrome or severe myoclonic epilepsy in infancy (SMEI) is an epileptic syndrome characterised by refractory epilepsy and intellectual disability, typically presenting with febrile and afebrile generalised and unilateral clonic/tonic-clonic seizures in the first year of life and other types of seizures appearing later in the course of the disease. Five adult patients with SMEI and SCN1A ...

Journal: :The Journal of neuroscience : the official journal of the Society for Neuroscience 2007
Raffaella Rusconi Paolo Scalmani Rita Restano Cassulini Giulia Giunti Antonio Gambardella Silvana Franceschetti Grazia Annesi Enzo Wanke Massimo Mantegazza

Familial epilepsies are often caused by mutations of voltage-gated Na+ channels, but correlation genotype-phenotype is not yet clear. In particular, the cause of phenotypic variability observed in some epileptic families is unclear. We studied Na(v)1.1 (SCN1A) Na+ channel alpha subunit M1841T mutation, identified in a family characterized by a particularly large phenotypic spectrum. The mutant ...

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