Read by QxMD icon Read

SCN5A Mutations

Jyh-Ming Jimmy Juang, Minoru Horie
In 1992, the Brugada syndrome (BrS) was recognized as a disease responsible for sudden cardiac death, characterized by a right bundle-branch block with ST segment elevation in the leads V1 and V2. This syndrome is highly associated with sudden cardiac death, especially in young males. BrS is currently diagnosed in patients with ST-segment elevation showing type 1 morphology ≥ 2 mm in ≥1 leads among the right precordial leads V1 or V2 positioned in the 2nd, 3rd, or 4th intercostal space, and occurring either spontaneously or after a provocative drug test by the intravenous administration of Class I antiarrhythmic drugs...
October 2016: Journal of Arrhythmia
Maria Cecilia Gonzalez Corcia, Juan Sieira, Andrea Sarkozy, Carlo de Asmundis, Gian-Battista Chierchia, Jaime Hernandez Ojeda, Gudrun Pappaert, Pedro Brugada
AIMS: To investigate the clinical characteristics, prognoses, and presence of risk factors in young patients with Brugada syndrome (BS). METHODS AND RESULTS: A consecutive cohort of 128 young BS patients (≤25 years old at diagnosis) was analysed. Eighty-eight patients (69%) were asymptomatic, whereas 40 (31%) presented with clinical manifestations of BS. Markers of prognosis and risk were identified upon comparison of these two groups. A history of malignant syncope was strong predictors of ventricular arrhythmic events...
October 13, 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
Ehud Chorin, Dan Hu, Charles Antzelevitch, Aviram Hochstadt, Luiz Belardinelli, David Zeltser, Hector Barajas-Martinez, Uri Rozovski, Raphael Rosso, Arnon Adler, Jesaia Benhorin, Sami Viskin
BACKGROUND: The basic defect in long-QT syndrome type III (LQT3) is an excessive inflow of sodium current during phase 3 of the action potential caused by mutations in the SCN5A gene. Most sodium channel blockers reduce the early (peak) and late components of the sodium current (INa and INaL), but ranolazine preferentially reduces INaL. We, therefore, evaluated the effects of ranolazine in LQT3 caused by the D1790G mutation in SCN5A. METHODS AND RESULTS: We performed an experimental study of ranolazine in TSA201 cells expressing the D1790G mutation...
October 2016: Circulation. Arrhythmia and Electrophysiology
James Rush Priest, Charles Gawad, Kristopher M Kahlig, Joseph K Yu, Thomas O'Hara, Patrick M Boyle, Sridharan Rajamani, Michael J Clark, Sarah T K Garcia, Scott Ceresnak, Jason Harris, Sean Boyle, Frederick E Dewey, Lindsey Malloy-Walton, Kyla Dunn, Megan Grove, Marco V Perez, Norma F Neff, Richard Chen, Katsuhide Maeda, Anne Dubin, Luiz Belardinelli, John West, Christian Antolik, Daniela Macaya, Thomas Quertermous, Natalia A Trayanova, Stephen R Quake, Euan A Ashley
Somatic mosaicism, the occurrence and propagation of genetic variation in cell lineages after fertilization, is increasingly recognized to play a causal role in a variety of human diseases. We investigated the case of life-threatening arrhythmia in a 10-day-old infant with long QT syndrome (LQTS). Rapid genome sequencing suggested a variant in the sodium channel NaV1.5 encoded by SCN5A, NM_000335:c.5284G > T predicting p.(V1762L), but read depth was insufficient to be diagnostic. Exome sequencing of the trio confirmed read ratios inconsistent with Mendelian inheritance only in the proband...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
Shinichiro Okata, Shinsuke Yuasa, Tomoyuki Suzuki, Shogo Ito, Naomasa Makita, Tetsu Yoshida, Min Li, Junko Kurokawa, Tomohisa Seki, Toru Egashira, Yoshiyasu Aizawa, Masaki Kodaira, Chikaaki Motoda, Gakuto Yozu, Masaya Shimojima, Nozomi Hayashiji, Hisayuki Hashimoto, Yusuke Kuroda, Atsushi Tanaka, Mitsushige Murata, Takeshi Aiba, Wataru Shimizu, Minoru Horie, Kaichiro Kamiya, Tetsushi Furukawa, Keiichi Fukuda
SCN5A is abundant in heart and has a major role in INa. Loss-of-function mutation in SCN5A results in Brugada syndrome (BrS), which causes sudden death in adults. It remains unclear why disease phenotype does not manifest in the young even though mutated SCN5A is expressed in the young. The aim of the present study is to elucidate the timing of the disease manifestation in BrS. A gain-of-function mutation in SCN5A also results in Long QT syndrome type 3 (LQTS3), leading to sudden death in the young. Induced pluripotent stem cells (iPSCs) were generated from a patient with a mixed phenotype of LQTS3 and BrS with the E1784K SCN5A mutation...
September 28, 2016: Scientific Reports
U Lakshmanadoss, A Mertens, M Gallagher, I Kutinsky, B Williamson
Inherited arrhythmia syndromes are a known, albeit rare, cause of sudden cardiac arrest which may present with characteristic electrocardiogram changes in patients with structurally normal heart. There are a variety of distinct arrhythmogenic syndromes that arise from mutations in voltage gated sodium channels, resulting in either gain or loss of function. We describe a patient with a primary inherited arrhythmia syndrome which presented as sudden cardiac arrest. Further workup revealed that her arrest was due to a combination of Brugada syndrome and Long QT3 syndrome secondary to a deleterious mutation of voltage-gated, sodium channel, type V alpha subunit (SCN5A Thr1709Met)...
March 2016: Indian Pacing and Electrophysiology Journal
A L M J van der Knijff-van Dortmont, M Dirckx, J J Duvekot, J W Roos-Hesselink, A Gonzalez Candel, C D van der Marel, G P Scoones, V F R Adriaens, I J J Dons-Sinke
SCN5A gene mutations can lead to ion channel defects which can cause cardiac conduction disturbances. In the presence of specific ECG characteristics, this mutation is called Brugada syndrome. Many drugs are associated with adverse events, making anesthesia in patients with SCN5A gene mutations or Brugada syndrome challenging. In this case report, we describe a pregnant patient with this mutation who received epidural analgesia using low dose ropivacaine and sufentanil during labour.
2016: Case Reports in Anesthesiology
Michelle N Vazquez, Gabrielle Gold-von Simson
Brugada syndrome (BrS) is rare genetic disorder, which manifests as syncope or sudden death caused by polymorphic ventricular tachycardia. Diagnosis is based on symptoms and characteristic electrocardiography findings. Identification of mutations in SCN5A support the diagnosis, but the yield is low. According to experts, BrS patients with a history of cardiac arrest should have insertion of an automatic implantable cardiac defibrillator and asymptomatic patients can be managed conservatively. Treatment challenges occur in patients with "intermediate" clinical characteristics and in populations where there is paucity of data such as with neonates and children...
June 2013: Journal of Pediatric Genetics
Nobue Yagihara, Hiroshi Watanabe, Phil Barnett, Laetitia Duboscq-Bidot, Atack C Thomas, Ping Yang, Seiko Ohno, Kanae Hasegawa, Ryozo Kuwano, Stéphanie Chatel, Richard Redon, Jean-Jacques Schott, Vincent Probst, Tamara T Koopmann, Connie R Bezzina, Arthur A M Wilde, Yukiko Nakano, Takeshi Aiba, Yoshihiro Miyamoto, Shiro Kamakura, Dawood Darbar, Brian S Donahue, Daichi Shigemizu, Toshihiro Tanaka, Tatsuhiko Tsunoda, Masayoshi Suda, Akinori Sato, Tohru Minamino, Naoto Endo, Wataru Shimizu, Minoru Horie, Dan M Roden, Naomasa Makita
BACKGROUND: Mutations in the coding sequence of SCN5A, which encodes the cardiac Na(+) channel α subunit, have been associated with inherited susceptibility to various arrhythmias. Variable expression of SCN5A is a possible mechanism responsible for this pleiotropic effect; however, it is unknown whether variants in the promoter and regulatory regions of SCN5A also modulate the risk of arrhythmias. METHODS AND RESULTS: We resequenced the core promoter region of SCN5A and the regulatory regions of SCN5A transcription in 1298 patients with arrhythmia phenotypes (atrial fibrillation, n=444; sinus node dysfunction, n=49; conduction disease, n=133; Brugada syndrome, n=583; and idiopathic ventricular fibrillation, n=89)...
September 2016: Journal of the American Heart Association
Edelmann J, Dobosz T, Sobieszczanska M, Kawecka-Negrusz M, Dreßler J, Nastainczyk-Wulf M
Congenital long QT-syndrome (LQTS) is an inherited cardiac arrhythmia, which is characterized by a prolonged QT interval which predisposes to sudden cardiac death due to ventricular arrhythmias. The altered functions are based on different mutations in LQTS-associated genes. In this study, we performed a mutation analysis for the detection of 125 LQTS-associated single nucleotide polymorphisms (SNPs) focused on the genes KCNQ1, KCNH2, and SCN5A by using the SNaPshot multiplex minisequencing technique. Furthermore, we investigated 152 autopsy-negative cases from younger adults and infants, as well as samples from patients with clinically suspicion for LQTS, in which we found two types of variations...
September 9, 2016: International Journal of Legal Medicine
Isik Turker, Takeru Makiyama, Matteo Vatta, Hideki Itoh, Takeshi Ueyama, Akihiko Shimizu, Tomohiko Ai, Minoru Horie
BACKGROUND: Class IC antiarrhythmic agents may induce acquired forms of Brugada Syndrome. We have identified a novel mutation in SCN5A, the gene that encodes the α-subunit of the human cardiac sodium channel (hNav1.5), in a patient who exhibited Brugada- type ECG changes during pharmacotherapy of atrial arrhythmias. OBJECTIVE: To assess whether the novel mutation p.V1328M can cause drug induced Brugada Syndrome. METHODS: Administration of pilsicainide, a class IC antiarrhythmic agent, caused Brugada- type ST elevation in a 66-year-old Japanese male who presented with paroxysmal atrial fibrillation (PAF), type I atrial flutter and inducible ventricular fibrillation (VF) during electrophysiological study...
2016: PloS One
Mariana Priganc, Michaela Zigová, Iveta Boroňová, Jarmila Bernasovská, Dana Dojčáková, Viktória Szabadosová, Marta Mydlárová Blaščáková, Iveta Tóthová, Ján Kmec, Ivan Bernasovský
OBJECTIVE: Mutations in ion channels genes are potential cause of cardiomyopathy. The SCN5A gene (sodium channel, voltage gated, type V alpha subunit gene; 3p21) belongs to the family of cardiac sodium channel genes. Mutations in SCN5A gene lead to decreased Na+ current and ion unbalance. The SCN5A gene mutations are found in approximately 2% of patients with dilated cardiomyopathy (DCM), and they may be potential phenotype modifiers in hypertrophic cardiomyopathy (HCM). The role of SCN5A gene mutations in cardiomyopathy is not fully elucidated...
August 24, 2016: Journal of Clinical Laboratory Analysis
Bijal Vyas, Ratna D Puri, Narayanan Namboodiri, Renu Saxena, Mohan Nair, Prahlad Balakrishnan, M P Jayakrishnan, Ameya Udyavar, Ravi Kishore, Ishwar C Verma
BACKGROUND: Long QT syndromes (LQTS) are characterized by prolonged QTc interval on electrocardiogram (ECG) and manifest with syncope, seizures or sudden cardiac death. Long QT 1-3 constitute about 75% of all inherited LQTS. We classified a cohort of Indian patients for the common LQTS based on T wave morphology and triggering factors to prioritize the gene to be tested. We sought to identify the causative mutations and mutation spectrum, perform genotype-phenotype correlation and screen family members...
January 2016: Indian Pacing and Electrophysiology Journal
Christiaan C Veerman, Isabella Mengarelli, Kaomei Guan, Michael Stauske, Julien Barc, Hanno L Tan, Arthur A M Wilde, Arie O Verkerk, Connie R Bezzina
Brugada syndrome (BrS) is a rare cardiac rhythm disorder associated with sudden cardiac death. Mutations in the sodium channel gene SCN5A are found in ~20% of cases while mutations in other genes collectively account for <5%. In the remaining patients the genetic defect and the underlying pathogenic mechanism remain obscure. To provide insight into the mechanism of BrS in individuals without identified mutations, we here studied electrophysiological properties of cardiomyocytes (CMs) generated from human induced pluripotent stem cells (hiPSCs) from 3 BrS patients who tested negative for mutations in the known BrS-associated genes...
2016: Scientific Reports
Wenqing Wu, Li Tian, Jinshan Ke, Yi Sun, Ruixia Wu, Jianfang Zhu, Qinmei Ke
INTRODUCTION: Inconsistent results have been reported about the risk stratification of patients with Brugada syndrome. We have summarized the evidence regarding the strength of association between 6 risk factors (family history of sudden cardiac death [SCD] or syncope, inducible ventricular arrhythmias on electrophysiology study [EPS], spontaneous type 1 Brugada electrocardiogram [ECG], male sex, family history of SCD, and sodium voltage-gated channel alpha subunit 5 [SCN5A] gene mutation) and subsequent cardiac events in Brugada syndrome patients...
July 2016: Medicine (Baltimore)
Keith Suarez, Maria Blazo, Javier E Banchs
No abstract text is available yet for this article.
July 29, 2016: Journal of Cardiovascular Electrophysiology
Christian Veltmann, Hector Barajas-Martinez, Christian Wolpert, Martin Borggrefe, Rainer Schimpf, Ryan Pfeiffer, Gabriel Cáceres, Elena Burashnikov, Charles Antzelevitch, Dan Hu
BACKGROUND: Phenotypic overlap of type 3 long QT syndrome (LQT3), Brugada syndrome (BrS), cardiac conduction disease (CCD), and sinus node dysfunction (SND) is observed with SCN5A mutations. SCN5A-E1784K is the most common mutation associated with BrS and LQTS3. The present study examines the genotype-phenotype relationship in a large family carrying SCN5A-E1784K and SCN5A-H558R polymorphism. METHODS AND RESULTS: Clinical work-up, follow-up, and genetic analysis were performed in 35 family members...
July 2016: Journal of the American Heart Association
Vincent Portero, Solena Le Scouarnec, Zeineb Es-Salah-Lamoureux, Sophie Burel, Jean-Baptiste Gourraud, Stéphanie Bonnaud, Pierre Lindenbaum, Floriane Simonet, Jade Violleau, Estelle Baron, Eléonore Moreau, Carol Scott, Stéphanie Chatel, Gildas Loussouarn, Thomas O'Hara, Philippe Mabo, Christian Dina, Hervé Le Marec, Jean-Jacques Schott, Vincent Probst, Isabelle Baró, Céline Marionneau, Flavien Charpentier, Richard Redon
BACKGROUND: The Brugada syndrome is an inherited cardiac arrhythmia associated with high risk of sudden death. Although 20% of patients with Brugada syndrome carry mutations in SCN5A, the molecular mechanisms underlying this condition are still largely unknown. METHODS AND RESULTS: We combined whole-exome sequencing and linkage analysis to identify the genetic variant likely causing Brugada syndrome in a pedigree for which SCN5A mutations had been excluded. This approach identified 6 genetic variants cosegregating with the Brugada electrocardiographic pattern within the pedigree...
June 2016: Journal of the American Heart Association
Beatriz Ortiz-Bonnin, Susanne Rinné, Robin Moss, Anne K Streit, Michael Scharf, Katrin Richter, Anika Stöber, Arne Pfeufer, Gunnar Seemann, Stefan Kääb, Britt-Maria Beckmann, Niels Decher
SCN5A encodes for the α-subunit of the cardiac voltage-gated sodium channel Nav1.5. Gain-of-function mutations in SCN5A are related to congenital long QT syndrome (LQTS3) characterized by delayed cardiac repolarization, leading to a prolonged QT interval in the ECG. Loss-of-function mutations in SCN5A are related to Brugada syndrome (BrS), characterized by an ST-segment elevation in the right precordial leads (V1-V3). The aim of this study was the characterization of a large set of novel SCN5A variants found in patients with different cardiac phenotypes, mainly LQTS and BrS...
August 2016: Pflügers Archiv: European Journal of Physiology
Jinxiang Zheng, Feng Zhou, Terry Su, Lei Huang, Yeda Wu, Kun Yin, Qiuping Wu, Shuangbo Tang, Jonathan C Makielski, Jianding Cheng
Increasing evidence observed in clinical phenotypes show that abrupt breathing disorders during sleep may play an important role in the pathogenesis of sudden unexplained nocturnal death syndrome (SUNDS). The reported Brugada syndrome causing mutation R1512W in cardiac sodium channel α subunit encoded gene SCN5A, without obvious loss of function of cardiac sodium channel in previous in vitro study, was identified as the first genetic cause of Chinese SUNDS by us. The R1512W carrier was a 38-year-old male SUNDS victim who died suddenly after tachypnea in nocturnal sleep without any structural heart disease...
June 2016: Medicine (Baltimore)
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"