scholarly journals Novel SCN5A mutation associated with idiopathic ventricular fibrillation due to subclinical Brugada syndrome

2011 ◽  
Vol 2 (1) ◽  
pp. 1
Author(s):  
Juan Jiménez-Jáimez ◽  
Miguel Álvarez-López ◽  
Luis Tercedor-Sánchez ◽  
Pablo Santiago ◽  
Maria Algarra ◽  
...  
Keyword(s):  
Ventricular Fibrillation ◽  
Brugada Syndrome ◽  
Idiopathic Ventricular Fibrillation ◽  
Scn5a Mutation

A novel SCN5A mutation associated with idiopathic ventricular fibrillation without typical ECG findings of Brugada syndrome

FEBS Letters ◽  
2000 ◽  
Vol 479 (1-2) ◽  
pp. 29-34 ◽  
Author(s):  
Jun Akai ◽  
Naomasa Makita ◽  
Harumizu Sakurada ◽  
Nobumasa Shirai ◽  
Kazuo Ueda ◽  
...  
Keyword(s):  
Ventricular Fibrillation ◽  
Brugada Syndrome ◽  
Idiopathic Ventricular Fibrillation ◽  
Scn5a Mutation

Abstract 15210: Do Idiopathic Ventricular Fibrillation and Brugada Syndrome Patients Have Favor Outcomes in the Targeted Temperature Management Era?

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Eisuke Kagawa ◽  
Masaya Kato ◽  
Noboru Oda ◽  
Eiji Kunita ◽  
Michiaki NAGAI ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Survival Rate ◽  
Ventricular Fibrillation ◽  
Brugada Syndrome ◽  
Cardiac Dysfunction ◽  
Targeted Temperature Management ◽  
Temperature Management ◽  
Circulatory Support ◽  
Idiopathic Ventricular Fibrillation ◽  
Coronary Syndrome

Introduction: Idiopathic ventricular fibrillation (IVF) including Brugada syndrome (BS) is one of causes of cardiac arrest without prior overt cardiac dysfunction. Hypothesis: We assessed the hypothesis that patents of IVF had favor outcomes than those of non-IVF after cardiac arrest treated with targeted temperature management (TTM). Methods: Patients who were treated with TTM after cardiac arrest between 2000 and 2019 were enrolled in the study. Patients were divided into 2 groups according to whether the patients were diagnosed as IVF or not. The patients treated with TTM were routinely performed coronary angiography. Results: Among the study patients (N = 306), 35 (11%) patients were IVF and 7 were BS. The patients of the IVF group were significantly younger (median 53 y vs. 64 y) than those of the non-IVF group. The prevalence of initial rhythm was shockable (69% vs. 47%, P = 0.02) was significantly higher in the patients of the IVF group than those of the non-IVF group. Among the patients in the non-IVF group, 114 patients (42%) were diagnosed as acute coronary syndrome and 93 patients (35%) were treated with coronary revascularization. The prevalence of male sex (77% vs 74%, P = 0.70) and witnessed to arrest (80% vs. 81%, P = 0.87), and low-flow time (29 min vs. 38 min [20 - 43 min vs. 21 - 52 min, P = 0.15]) were similar between the 2 groups. The prevalence of performing extracorporeal resuscitation (9% s 43%, P < 0.001) were lower in the patients of the IVF group. The 8-y survival rate were shown in the figure. All of the BS patients were witnessed arrest and were discharged without severe neurological deficit. The IVF as the cause of arrest was independently associated with 8-y survival. Conclusions: The patients of IVF had favor outcomes than those of non-VF. One of causes may be the lower prevalence of requiring extracorporeal circulatory support due to less cardiac dysfunction. The patients of BS had the tendency toward higher survival rate than those of non-BS IVF patients.

Abstract 5676: Elevated Oxidative Stress is Associated with Ventricular Fibrillation Episode in Patients with Brugada Syndrome without SCN5A Mutation

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Masamichi Tanaka ◽  
Keiko Ohgou ◽  
Koji Nakagawa ◽  
Takeshi Tada ◽  
Masato Murakami ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Risk Factor ◽  
Ventricular Fibrillation ◽  
Brugada Syndrome ◽  
Endomyocardial Biopsy ◽  
Heart Diseases ◽  
Multivariable Analysis ◽  
Pathophysiological Mechanism ◽  
Normal Heart ◽  
Scn5a Mutation

Background; Brugada Syndrome (BS) is a disease known to cause ventricular fibrillation (VF) with structurally normal heart. Gene mutation (i.e. SCN5A) has been proposed to be related to the development of BS and VF. However, the pathophysiological mechanism associated with VF development without SCN5A mutation has not been studied yet. Oxidative stress is a common disorder that is related to many heart diseases. We have previously demonstrated that oxidative stress is closely linked to the arrhythmic development. Accordingly, we examined 4-hydroxy-2-nonenal (HNE) modified protein, which is a common mediator of oxidative stress in the myocardium, and VF episodes in patients with BS. Methods; We collected sixty-eight BS patients that underwent right ventricular endomyocardial biopsy (66 males, 2 female; mean age 49.0±11.6 years old). VF was documented in 11 and SCN5A mutation was detected in 14 patients. Biopsy samples were processed for histology [Masson’s trichrome staining for fibrosis, immuno staining for CD45, CD68, and HNE modified protein]. All results from histology were compared with VF episodes. We also performed the analysis in VF patients with (n=14) or without SCN5A mutations (n=54). Results: HNE positive area was significantly larger in VF patients [VF(+): 16.3±10.5, VF(−): 9.3±5.7%: P=0.029]. All other parameters (fibrosis area, CD45, and CD68) were not different between the groups. In multivariable analysis, HNE positive area was most important risk factor of VF development in patients without SCN5A mutation (P=0.004). Conclusions ; These data suggested that oxidative stress is associated with VF development in BS patients, especially in patients without SCN5A mutation.

Abstract 5317: Identification and Characterization of a Novel Susceptibility Gene, SCN3B, for Idiopathic Ventricular Fibrillation

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Carmen R Valdivia ◽  
Argelia Mereidos-Domingo ◽  
Thimothy J Algiers ◽  
Michael J Ackerman ◽  
Jonathan C Makielski
Keyword(s):  
Ventricular Fibrillation ◽  
Sodium Channel ◽  
Brugada Syndrome ◽  
Mutational Analysis ◽  
Sodium Current ◽  
Susceptibility Gene ◽  
Site Directed Mutagenesis ◽  
Macromolecular Complex ◽  
Patch Clamp Technique ◽  
Idiopathic Ventricular Fibrillation

Background: Mutations in the Na V 1.5 sodium channel macromolecular complex have been identified in some cases classified as idiopathic ventricular fibrillation (IVF). IVF and Brugada syndrome (BrS) are partially overlapping syndromes. Here, we report a mutation in SCN3B- encoded sodium channel β3 subunit as a novel pathogenic mechanism for IVF. Methods: Comprehensive open reading frame mutational analysis of SCN5A, GPD1L, and the beta subunit genes ( SCN1–4B ) was performed using PCR, DHPLC, and direct DNA sequencing of DNA extracted from a 20-year-old patient diagnosed with IVF. The SCN3B mutation was made by site directed mutagenesis and co-transfected with SCN5A into HEK-293 cells for functional chraracterization using the patch clamp technique. Results: A novel missense mutation, V54G-SCN3B, was identified in a 20-year-old male following collapse and external defibrillation from VF. After recovery, there was no detectable electrocardiographic abnormality. Imaging studies demonstrated a structurally normal heart, and the patient was diagnosed with IVF. The mutation was absent in 800 reference alleles and involved a highly conserved residue in the extracellular domain of the beta 3 subunit. No other mutations were identified in the 5 other genes. HEK cells expressing SCN5A and either WT-, or V54G-SCN3B were studied 24 hours after transfection. Cells expressing V54G-SCN3B showed significant decrease in sodium current density of 60±20 pA/pF compared to 203±35 pA/pF in WT-SCN3B (n=14–19). In addition V54G-SCN3B significantly shifted the activation curve +5 mV without affecting inactivation. Conclusions: This study provides the first molecular and cellular evidence implicating SCN3B in IVF. Given the marked loss-of-function to the sodium channel by V54G-SCN3B and the overlap between IVF and BrS, it will be interesting to determine whether mutations in SCN3B explain some cases of genotype negative Brugada syndrome.

Accelerated inactivation in a mutant Na+channel associated with idiopathic ventricular fibrillation

2001 ◽  
Vol 280 (1) ◽  
pp. H354-H360 ◽  
Author(s):  
Xiaoping Wan ◽  
Shenghan Chen ◽  
Azita Sadeghpour ◽  
Qing Wang ◽  
Glenn E. Kirsch
Keyword(s):  
Ventricular Fibrillation ◽  
Infant Death ◽  
Brugada Syndrome ◽  
Sudden Infant Death ◽  
Na Channel ◽  
Sudden Infant ◽  
Gene Encoding ◽  
Human Embryonic Kidney Cells ◽  
Idiopathic Ventricular Fibrillation ◽  
Adults And Children

Idiopathic ventricular fibrillation (IVF) can cause sudden death in both adults and children. One form of IVF (Brugada syndrome), characterized by S-T segment elevation (STE) in the electrocardiogram, has been linked to mutations of SCN5A, the gene encoding the voltage-gated cardiac Na+ channel. A missense mutation of SCN5A that substitutes glutamine for leucine at codon 567 (L567Q, in the cytoplasmic linker between domains I and II) is identified with sudden infant death and Brugada syndrome in one family. However, neither the functional effect of the L567Q mutation nor the molecular mechanism underlying the pathogenicity of the mutation is known. Patch-clamp analysis of L567Q channels expressed in human embryonic kidney cells revealed a marked acceleration and a negative shift in the voltage dependence of inactivation. Unlike other Brugada mutations, this phenotype was expressed independently of temperature or auxiliary β1-subunits. These results support a proposed linkage between Brugada syndrome and some instances of sudden infant death and the hypothesis that reduced Na+ conductance is the primary cause of IVF with STE.

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