scholarly journals Neuronal Sodium-Channel α1-Subunit Mutations in Generalized Epilepsy with Febrile Seizures Plus

2001 ◽  
Vol 68 (4) ◽  
pp. 859-865 ◽  
Author(s):  
R.H. Wallace ◽  
I.E. Scheffer ◽  
S. Barnett ◽  
M. Richards ◽  
L. Dibbens ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Febrile Seizures ◽  
Generalized Epilepsy ◽  
Febrile Seizures Plus ◽  
Α1 Subunit

Functional characterization of the D188V mutation in neuronal voltage-gated sodium channel causing generalized epilepsy with febrile seizures plus (GEFS)

2003 ◽  
Vol 53 (1-2) ◽  
pp. 107-117 ◽  
Author(s):  
Patrick Cossette ◽  
Andrew Loukas ◽  
Ronald G. Lafrenière ◽  
Daniel Rochefort ◽  
Eric Harvey-Girard ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Functional Characterization ◽  
Febrile Seizures ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated ◽  
Generalized Epilepsy ◽  
Febrile Seizures Plus

scholarly journals Functional and Biochemical Analysis of a Sodium Channel β1 Subunit Mutation Responsible for Generalized Epilepsy with Febrile Seizures Plus Type 1

2002 ◽  
Vol 22 (24) ◽  
pp. 10699-10709 ◽  
Author(s):  
Laurence S. Meadows ◽  
Jyoti Malhotra ◽  
Andrew Loukas ◽  
Veena Thyagarajan ◽  
Kristin A. Kazen-Gillespie ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Biochemical Analysis ◽  
Febrile Seizures ◽  
Generalized Epilepsy ◽  
Febrile Seizures Plus

Increased Neuronal Firing in Computer Simulations of Sodium Channel Mutations That Cause Generalized Epilepsy With Febrile Seizures Plus

2004 ◽  
Vol 91 (5) ◽  
pp. 2040-2050 ◽  
Author(s):  
Jay Spampanato ◽  
Ildiko Aradi ◽  
Ivan Soltesz ◽  
Alan L. Goldin
Keyword(s):  
Action Potential ◽  
Sodium Channel ◽  
Febrile Seizures ◽  
Neuronal Firing ◽  
Voltage Gated Sodium Channel ◽  
Single Action ◽  
Voltage Gated ◽  
Single Action Potential ◽  
Generalized Epilepsy ◽  
Febrile Seizures Plus

Generalized epilepsy with febrile seizures plus (GEFS+) is an autosomal dominant familial syndrome with a complex seizure phenotype. It is caused by mutations in one of 3 voltage-gated sodium channel subunit genes ( SCN1B, SCN1A, and SCN2A) and the GABAA receptor γ2 subunit gene ( GBRG2). The biophysical characterization of 3 mutations (T875M, W1204R, and R1648H) in SCN1A, the gene encoding the CNS voltage-gated sodium channel α subunit Nav1.1, demonstrated a variety of functional effects. The T875M mutation enhanced slow inactivation, the W1204R mutation shifted the voltage dependency of activation and inactivation in the negative direction, and the R1648H mutation accelerated recovery from inactivation. To determine how these changes affect neuronal firing, we used the NEURON simulation software to design a computational model based on the experimentally determined properties of each GEFS+ mutant sodium channel and a delayed rectifier potassium channel. The model predicted that W1204R decreased the threshold, T875M increased the threshold, and R1648H did not affect the threshold for firing a single action potential. Despite the different effects on the threshold for firing a single action potential, all of the mutations resulted in an increased propensity to fire repetitive action potentials. In addition, each mutation was capable of driving repetitive firing in a mixed population of mutant and wild-type channels, consistent with the dominant nature of these mutations. These results suggest a common physiological mechanism for epileptogenesis resulting from sodium channel mutations that cause GEFS+.

scholarly journals Novel mutation of SCN9A gene causing generalized epilepsy with febrile seizures plus in a Chinese family

2020 ◽  
Vol 41 (7) ◽  
pp. 1913-1917 ◽  
Author(s):  
Tian Zhang ◽  
Mingwu Chen ◽  
Angang Zhu ◽  
Xiaoguang Zhang ◽  
Tao Fang
Keyword(s):  
Sodium Channel ◽  
Febrile Seizures ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Gene Encoding ◽  
Voltage Gated Sodium Channel ◽  
Α Subunit ◽  
Voltage Gated ◽  
Generalized Epilepsy ◽  
Febrile Seizures Plus

Abstract Generalized epilepsy with febrile seizures plus (GEFS+) is a complex familial epilepsy syndrome. It is mainly caused by mutations in SCN1A gene, encoding type 1 voltage-gated sodium channel α-subunit (NaV1.1), and GABRA1 gene, encoding the α1 subunit of the γ-aminobutyric acid type A (GABAA) receptor, while seldom related with SCN9A gene, encoding the voltage-gated sodium channel NaV1.7. In this study, we investigated a Chinese family with an autosomal dominant form of GEFS+. DNA sequencing of the whole coding region revealed a novel heterozygous nucleotide substitution (c.5873A>G) causing a missense mutation (p.Y1958C). This mutation was predicted to be deleterious by three different bioinformatics programs (The polyphen2, SIFT, and MutationTaster). 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.

Generalized epilepsy with febrile seizures plus: Mutation of the sodium channel subunit SCN1B

Neurology ◽  
2002 ◽  
Vol 58 (9) ◽  
pp. 1426-1429 ◽  
Author(s):  
R. H. Wallace ◽  
I. E. Scheffer ◽  
G. Parasivam ◽  
S. Barnett ◽  
G. B. Wallace ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Febrile Seizures ◽  
Generalized Epilepsy ◽  
Febrile Seizures Plus
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