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.

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

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 Trafficking and Function of the Voltage-Gated Sodium Channel β2 Subunit

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 604 ◽  
Author(s):  
Eric Cortada ◽  
Ramon Brugada ◽  
Marcel Verges
Keyword(s):  
Sodium Channel ◽  
Electrical Coupling ◽  
Surface Expression ◽  
Current Data ◽  
Cell Surface Expression ◽  
Gene Encoding ◽  
Voltage Gated Sodium Channel ◽  
Α Subunit ◽  
Voltage Gated

The voltage-gated sodium channel is vital for cardiomyocyte function, and consists of a protein complex containing a pore-forming α subunit and two associated β subunits. A fundamental, yet unsolved, question is to define the precise function of β subunits. While their location in vivo remains unclear, large evidence shows that they regulate localization of α and the biophysical properties of the channel. The current data support that one of these subunits, β2, promotes cell surface expression of α. The main α isoform in an adult heart is NaV1.5, and mutations in SCN5A, the gene encoding NaV1.5, often lead to hereditary arrhythmias and sudden death. The association of β2 with cardiac arrhythmias has also been described, which could be due to alterations in trafficking, anchoring, and localization of NaV1.5 at the cardiomyocyte surface. Here, we will discuss research dealing with mechanisms that regulate β2 trafficking, and how β2 could be pivotal for the correct localization of NaV1.5, which influences cellular excitability and electrical coupling of the heart. Moreover, β2 may have yet to be discovered roles on cell adhesion and signaling, implying that diverse defects leading to human disease may arise due to β2 mutations.

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

Identification of a Novel Nonsense Variant in the SCN1A Gene that Causes Febrile Seizure Disorder

2017 ◽  
Vol 16 (04) ◽  
pp. 236-238
Author(s):  
Nabila MarchoudI ◽  
Abdelfettah Rouissi ◽  
Jamal Fekkak ◽  
Farah Jouali
Keyword(s):  
Febrile Seizure ◽  
Febrile Seizures ◽  
Seizure Disorder ◽  
Gene Encoding ◽  
Seizure Disorders ◽  
Severe Myoclonic Epilepsy ◽  
Epilepsy Gene ◽  
Generalized Epilepsy ◽  
Febrile Seizures Plus ◽  
Scn1a Gene

AbstractThe SCN1A gene, encoding for the voltage-gated sodium channel Nav1.1, is the most clinically relevant epilepsy gene, with most mutations having been documented in a spectrum of epilepsy syndromes, ranging from the relatively benign generalized epilepsy with febrile seizures plus (GEFS+) to severe myoclonic epilepsy in infancy (SMEI), and other rare febrile seizure disorders. To date, more than 1,250 mutations in SCN1A have been linked to epilepsy. In this case, we describe a novel nonsense pathogenic variant (NM_001202435.1; c.327C > G) in SCN1A in a 10-month Moroccan infant with febrile seizure disorder.

Failure to find evidence for association between voltage-gated sodium channel gene SCN2A variants and febrile seizures in humans

2002 ◽  
Vol 329 (2) ◽  
pp. 249-251 ◽  
Author(s):  
Junko Nakayama ◽  
Nao Yamamoto ◽  
Kenzo Hamano ◽  
Nobuaki Iwasaki ◽  
Masayasu Ohta ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Febrile Seizures ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated ◽  
Channel Gene ◽  
Sodium Channel Gene

The voltage-gated sodium channel gene SCN2A and idiopathic generalized epilepsy

2001 ◽  
Vol 47 (3) ◽  
pp. 243-246 ◽  
Author(s):  
Karsten Haug ◽  
Kerstin Hallmann ◽  
Johannes Rebstock ◽  
Joern Dullinger ◽  
Sabine Muth ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Idiopathic Generalized Epilepsy ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated ◽  
Channel Gene ◽  
Sodium Channel Gene ◽  
Generalized Epilepsy
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