AI Article Synopsis
- The study aimed to understand how the SCN5A sodium ion channel is involved in dilated cardiomyopathy (DCM) and its implications for arrhythmias.
- Researchers analyzed genetic samples from 289 DCM families, identifying five unique SCN5A mutations, three of which were novel.
- A significant 93% of mutation carriers experienced arrhythmias, indicating a strong link between SCN5A mutations and arrhythmic conditions, with potential implications for clinical diagnosis and treatment.
Article Abstract
Objectives: The aim of this study was to discern the role of the cardiac voltage-gated sodium ion channel SCN5A in the etiology of dilated cardiomyopathy (DCM).
Background: Dilated cardiomyopathy associates with mutations in the SCN5A gene, but the frequency, phenotype, and causative nature of these associations remain the focus of ongoing investigation.
Methods: Since 1991, DCM probands and family members have been enrolled in the Familial Cardiomyopathy Registry and extensively evaluated by clinical phenotype. Genomic deoxyribonucleic acid samples from 338 individuals among 289 DCM families were obtained and screened for SCN5A mutations by denaturing high-performance liquid chromatography and sequence analysis.
Results: We identified 5 missense SCN5A mutations among our DCM families, including novel mutations E446K, F1520L, and V1279I, as well as previously reported mutations D1275N and R222Q. Of 15 SCN5A mutation carriers in our study, 14 (93%) manifested arrhythmia: supraventricular arrhythmia (13 of 15), including sick sinus syndrome (5 of 15) and atrial fibrillation (9 of 15), ventricular tachycardia (5 of 15), and conduction disease (9 of 15).
Conclusions: Mutations in SCN5A were detected in 1.7% of DCM families. Two-thirds (6 of 9) of all reported DCM mutations in SCN5A localize to the highly conserved homologous S3 and S4 transmembrane segments, suggesting a shared mechanism of disruption of the voltage-sensing mechanism of this channel leading to DCM. Not surprisingly, SCN5A mutation carriers show a strong arrhythmic pattern that has clinical and diagnostic implications.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9689753 | PMC |
| http://dx.doi.org/10.1016/j.jacc.2010.09.084 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
[Clinical and electrocardiographic characteristics of carriers with SCN5A mutations and non-SCN5A mutations in fever-induced Brugada syndrome].
Zhonghua Xin Xue Guan Bing Za Zhi
December 2024
Department of Cardiology and Cardiovascular Research Institute, Renmin Hospital of Wuhan University, Hubei Key Laboratory of Cardiology, Wuhan430060, China.
To investigate the differences in clinical and electrocardiographic characteristics between carriers of SCN5A mutations and non-SCN5A mutations in fever-induced Brugada syndrome. This study is a retrospective cohort study. A total of 263 patients with fever-induced Brugada syndrome who were admitted to Renmin Hospital of Wuhan University from January 2000 to December 2023 were selected.
View Article and Find Full Text PDFWe present a case of HCN4 gene mutation presenting with atrial standstill and stroke in the young.
View Article and Find Full Text PDFValidation and clinical implications of higher intercostal space electrocardiography in the patient with Brugada syndrome in Taiwan (SADS-TW BrS registry).
J Formos Med Assoc
December 2024
Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Electronic address:
Background: Diagnosis of Brugada syndrome (BrS) is based on type 1 morphology (coved type) in electrocardiograms from standard (4) or higher (2 or 3) intercostal spaces (ICSs). However, the clinical implications of being diagnosed only at higher ICSs remains poorly understood. We aimed to investigate the diagnostic accuracy of higher ICS leads in the Taiwanese Brugada syndrome population and clarify if there is any difference in clinical presentation.
View Article and Find Full Text PDFThe sodium/glucose cotransporter 2 inhibitor Empagliflozin inhibits long QT 3 late sodium currents in a mutation specific manner.
J Mol Cell Cardiol
January 2025
Department of Pharmacology, Alberta Diabetes Institute, Faculty of Medicine and Dentistry, University of Alberta, 7-55 Medical Sciences Building, Edmonton T6G 2H7, Alberta, Canada. Electronic address:
Article Synopsis
- Sodium/glucose cotransporter 2 inhibitors (SGLT2is), such as empagliflozin, show potential heart protection benefits in individuals with or without diabetes and can inhibit a key cardiac sodium current linked to congenital long QT syndrome type 3 (LQT3).
- Researchers used the whole-cell patch-clamp technique to study how empagliflozin affects late sodium current (late I) in various LQT3 mutations of the Nav1.5 channel.
- Empagliflozin specifically inhibited late I in certain mutations without altering channel kinetics, suggesting it could be an effective targeted treatment for patients with LQT3 mutations in the inactivation gate area.
The Yield of Genetic Testing and Putative Genetic Factors of Disease Heterogeneity in Long QT Syndrome Patients.
Int J Mol Sci
November 2024
National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia.
Article Synopsis
- * Among 82 LQTS patients, a 75% diagnostic yield was found in those with high Schwartz scores, while 50% of those with lower scores (<3.5) were diagnosed through broader genetic testing.
- * The findings suggest that the existing LQTS genetic diagnosis framework may not effectively capture cases with lower Schwartz scores, and additional rare variants could indicate more severe disease, pointing towards the need for improved referral criteria.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!