Nav1.5/R1193Q polymorphism is associated with both long QT and Brugada syndromes

Huang, Hai; Zhao, Juan; Barrane, Fatima-Zahra; Champagne, Jean; Chahine, Mohamed

doi:10.1016/s0828-282x(06)70915-1

Cited by 48 publications

(40 citation statements)

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“…Indeed, a shift of 5 mV of steady-state inactivation to more hyperpolarized voltages observed with R1193Q may explain the typical Brugada-associated 'loss of function' of sodium current. Meanwhile, the observation of a residual current also explains the typical 'gain of function' of sodium current observed in the long QT syndrome type 3 (16). Interestingly, the R1193Q mutation we found caused both BS and long QT syndrome in one patient, but only BS in the other.…”

Section: Discussionsupporting

confidence: 65%

“…The ultimate answer probably lies in a more comprehensive approach and a more precise understanding of the molecular genetics and their associated electrophysiological abnormalities. Two cases of BS with a heterozygous mutation (R1193Q) polymorphism associated with both long QT syndrome and BS were reported by our group (16). Indeed, a shift of 5 mV of steady-state inactivation to more hyperpolarized voltages observed with R1193Q may explain the typical Brugada-associated 'loss of function' of sodium current.…”

Section: Discussionmentioning

confidence: 80%

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The Brugada syndrome in Canada: A unique French-Canadian experience

Champagne

Philippon

Gilbert

et al. 2007

Canadian Journal of Cardiology

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B rugada syndrome (BS) involves a cardiac sodium channel abnormality and is associated with a high risk of ventricular arrhythmias and sudden cardiac death in individuals with a structurally normal heart. BS is mainly recognized in the specialized electrophysiology community. Characteristic electrocardiograms (ECGs) show a typical pattern of a right bundle branch block-like complex and ST segment elevation in leads V1 to V3 (1,2). In a recent consensus statement (3), three types of repolarization patterns were recognized: type 1 is diagnostic of BS and is characterized by an elevated, coved ST segment of 2 mm or greater followed by a negative T wave ( Figure 1); type 2 has a saddleback appearance with a high takeoff ST segment elevation of 2 mm or greater followed by an ST elevation of 1 mm or greater and either a positive or a THE QUEBEC HEART INSTITUTE ©2007 Pulsus Group Inc. All rights reserved The Brugada syndrome (BS) is a clinical entity involving cardiac sodium channelopathy, typical electrocardiogram (ECG) changes and predisposition to ventricular arrhythmia. This syndrome is mainly recognized by specialized cardiologists and electrophysiologists. Data regarding BS largely come from multicentre registries or Asian countries. The present report describes the Quebec Heart Institute experience, including the clinical characteristics and prognosis of native French-Canadian subjects with the Brugada-type ECG pattern. METHODS AND RESULTS: BS has been diagnosed in 35 patients (mean age 51±12 years) at the Quebec Heart Institute since 2001. Patients were referred from primary care physicians for ECG abnormalities, syncope or ventricular arrhythmia, or were diagnosed incidentally on an ECG obtained for other purposes. The abnormal ECG was recognized after a syncopal spell in four patients and during family screening in four patients. All of the others were incidental findings following a routine ECG. No patient had a family history of sudden cardiac death at younger than 45 years of age. In this population, right bundle branch block pattern with more than 2 mm ST segment elevation in leads V1 to V3 was recorded spontaneously in 25 patients and was induced by sodium blockers in 10 patients. The sodium channel blocker test was performed in 21 patients and was positive in 18 patients (86%). An electrophysiological study was performed in 20 of 35 patients, during which ventricular fibrillation was induced in five patients; three of the five patients were previously asymptomatic. An implantable cardioverter-defibrillator was implanted in six of 35 patients (17%), including three of four patients with a history of syncope. A loop recorder was implanted in three patients. After a mean follow-up of 36±18 months, one patient died from a noncardiac cause and one patient (with a history of syncope) received an appropriate shock from his implantable cardioverter-defibrillator. No event occurred in the asymptomatic population. CONCLUSIONS: BS is present in the French-Canadian population and is probably under-recognized. Long-...

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 80%

The Brugada syndrome in Canada: A unique French-Canadian experience

Champagne

Philippon

Gilbert

et al. 2007

Canadian Journal of Cardiology

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“…The p.R1193Q polymorphism has been associated with cardiac electrical abnormalities, arrhythmia predisposition, unexplained sudden death, and an abnormal electrophysiological in vitro phenotype consistent with a cardiac channelopathy [12,13]. The p.R1193Q mutation has recently been identified in patients with acquired Brugada syndrome, long QT syndrome, and cardiac conductance disease [4,5,14].…”

Section: Discussionmentioning

confidence: 99%

The global distribution of the p.R1193Q polymorphism in the SCN5A gene

et al. 2016

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“…P1090L (identified in patients B10, B15, and B25) and R1193Q (identified in patients B02 and B24) are Asian-specific polymorphisms, 20,26,27) although R1193Q has also been reported as a BrS and LQTScausing mutation. 28,29) R1232W (identified in patient B15) was originally reported as a rare polymorphism.…”

Section: Discussionmentioning

confidence: 99%

Identification of Six Novel SCN5A Mutations in Japanese Patients With Brugada Syndrome

et al. 2011

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SummaryMutations in SCN5A are linked to Brugada syndrome in approximately 20% of all cases (BrS1). Several dozen distinct SCN5A mutations in BrS1 have been associated with the increased risk of cardiac arrhythmias. However, the genotype-phenotype relationship remains elusive. The current study analyzed the SCN5A gene to elucidate the potential variability of clinical features in Japanese BrS1 subjects. Subjects of the present study included 30 probands (25 male subjects, 45 ± 15 years of age) with Brugada-pattern ECG. Seven patients had been resuscitated from cardiopulmonary arrest (CPA group). Another 10 patients had a history of syncope (Sy group), and 13 more remain asymptomatic (Asy group). We identified 8 different SCN5A mutations, including 6 novel mutations (CPA group: 1/7, Sy group: 3/10, Asy group: 4/13). An A735E mutation (located at segment (S)1 in domain (D)2) was identified in the CPA group. A novel splice acceptor site mutation (c.393-1c>t), which may produce a prematurely truncated protein, was identified in the Sy group. An E1784K mutation (C-terminus) and a novel mutation V1951M (C-terminus) were also identified in the Sy group. Four novel missense mutations, A586T (D1-D2 linker), R689H (D1-D2 linker), S1553R (S1-S2 in D4), and Q1706H (S5-Pore in D4) were identified in the Asy group. These data may help us understand the genetic heterogeneity of BrS1, which is more prevalent in Japanese than in whites and other ethnic groups. (Int Heart J 2011; 52: 27-31) Key words: Brugada syndrome, SCN5A, Mutation T he Brugada syndrome (BrS), characterized by ST-segment elevations in the right precordial ECG leads without structural heart disease, is a hereditable disease associated with an increased risk of sudden death due to polymorphic ventricular tachycardia or ventricular fibrillation (VF).1) Genetic analyses of BrS revealed that BrS is genetically heterogeneous, and is linked to at least 7 different genes. [2][3][4][5][6][7][8] Mutations in SCN5A, which encodes the pore-forming subunit of the cardiac voltage-gated sodium channel, have been associated with the major form of BrS (BrS1) in approximately 20% of cases. [9][10][11] The clinical severity of BrS may vary with the responsible genes and/or mutation sites, although the genotypephenotype relationship remains poorly characterized. The presence of SCN5A mutations is not related to the severity of the disease.9,10,12) However, Meregalli, et al have recently reported that the type of SCN5A mutation in BrS1 in European countries may determine the clinical severity.13) Because the clinical features of BrS vary among different ethnicities, 14,15) it is of great value to investigate the genotype-phenotype relationship of BrS in Asians in whom the ratio of BrS patients is relatively high compared to subjects from different ethnic backgrounds.In the present study, we analyzed the SCN5A gene to elucidate the potential variability of clinical features of BrS1 subjects recruited from Gunma University Hospital. Consequently, we identified 8 SCN5A mutations, incl...

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Nav1.5/R1193Q polymorphism is associated with both long QT and Brugada syndromes

Cited by 48 publications

References 20 publications

The Brugada syndrome in Canada: A unique French-Canadian experience

The Brugada syndrome in Canada: A unique French-Canadian experience

The global distribution of the p.R1193Q polymorphism in the SCN5A gene

Identification of Six Novel SCN5A Mutations in Japanese Patients With Brugada Syndrome

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