Coexistence of atrioventricular accessory pathways and drug-induced type 1 Brugada pattern.

Background: Atrial arrhythmias, particularly atrioventricular nodal reentrant tachycardia, can coexist with drug-induced type 1 Brugada electrocardiogram (ECG) pattern (DI-Type1-BrP). The present study was designed to determine the prevalence of DI-Type1-BrP in patients with atrioventricular accessory pathways (AV-APs) and to investigate the clinical, electrocardiographic, electrophysiologic, and genetic characteristics of these patients.

Methods: One-hundred twenty-four consecutive cases of AV-APs and 84 controls underwent an ajmaline challenge test to unmask DI-Type1-BrP.

Further Insights in the Most Common SCN5A Mutation Causing Overlapping Phenotype of Long QT Syndrome, Brugada Syndrome, and Conduction Defect.

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.

High prevalence of concealed Brugada syndrome in patients with atrioventricular nodal reentrant tachycardia.

Background: Atrioventricular nodal reentrant tachycardia (AVNRT) may coexist with Brugada syndrome (BrS).

Objectives: The present study was designed to determine the prevalence of drug-induced type 1 Brugada ECG pattern (concealed BrS) in patients presenting with clinical spontaneous AVNRT and to investigate their electrocardiographic, electrophysiological, and genetic characteristics.

Methods: Ninety-six consecutive patients without any sign of BrS on baseline electrocardiogram undergoing electrophysiological study and ablation for symptomatic, drug-resistant AVNRT and 66 control subjects underwent an ajmaline challenge to unmask BrS.

ABCC9 is a novel Brugada and early repolarization syndrome susceptibility gene.

Background: Genetic defects in KCNJ8, encoding the Kir6.1 subunit of the ATP-sensitive K(+) channel (I(K-ATP)), have previously been associated with early repolarization (ERS) and Brugada (BrS) syndromes. Here we test the hypothesis that genetic variants in ABCC9, encoding the ATP-binding cassette transporter of IK-ATP (SUR2A), are also associated with both BrS and ERS.

A novel rare variant in SCN1Bb linked to Brugada syndrome and SIDS by combined modulation of Na(v)1.5 and K(v)4.3 channel currents.

Background: Cardiac sodium channel β-subunit mutations have been associated with several inherited cardiac arrhythmia syndromes.

Objective: To identify and characterize variations in SCN1Bb associated with Brugada syndrome (BrS) and sudden infant death syndrome (SIDS).

Methods: All known exons and intron borders of the BrS-susceptibility genes were amplified and sequenced in both directions.

Long QT, syndactyly, joint contractures, stroke and novel CACNA1C mutation: expanding the spectrum of Timothy syndrome.

Timothy syndrome (TS) is an autosomal dominant condition with the constellation of features including prolonged QT interval, hand and foot abnormalities, and mental retardation or autism. Splawski et al. [2004] previously described two phenotypes associated with TS distinguished by two unique and different mutations within the CACNA1C gene.

Molecular genetic and functional association of Brugada and early repolarization syndromes with S422L missense mutation in KCNJ8.

Background: Adenosine triphosphate (ATP)-sensitive potassium cardiac channels consist of inward-rectifying channel subunits Kir6.1 or Kir6.2 (encoded by KCNJ8 or KCNJ11) and the sulfonylurea receptor subunits SUR2A (encoded by ABCC9).

LQT5 masquerading as LQT2: a dominant negative effect of KCNE1-D85N rare polymorphism on KCNH2 current.

Aims: KCNE1 encodes an auxiliary subunit of cardiac potassium channels. Loss-of-function variations in this gene have been associated with the LQT5 form of the long QT syndrome (LQTS), secondary to reduction of I(Ks) current. We present a case in which a D85N rare polymorphism in KCNE1 is associated with an LQT2 phenotype.

Overlapping LQT1 and LQT2 phenotype in a patient with long QT syndrome associated with loss-of-function variations in KCNQ1 and KCNH2.

Long QT syndrome (LQTS) is an inherited disorder characterized by prolonged QT intervals and potentially life-threatening arrhythmias. Mutations in 12 different genes have been associated with LQTS. Here we describe a patient with LQTS who has a mutation in KCNQ1 as well as a polymorphism in KCNH2.

Biophysical and molecular characterization of a novel de novo KCNJ2 mutation associated with Andersen-Tawil syndrome and catecholaminergic polymorphic ventricular tachycardia mimicry.

Background: Mutations in KCNJ2, the gene encoding the human inward rectifier potassium channel Kir2.1 (IK1 or IKir2.1), have been identified in Andersen-Tawil syndrome.

Mutations in the cardiac L-type calcium channel associated with inherited J-wave syndromes and sudden cardiac death.

Background: L-type calcium channel (LTCC) mutations have been associated with Brugada syndrome (BrS), short QT (SQT) syndrome, and Timothy syndrome (LQT8). Little is known about the extent to which LTCC mutations contribute to the J-wave syndromes associated with sudden cardiac death.

Objective: The purpose of this study was to identify mutations in the α1, β2, and α2δ subunits of LTCC (Ca(v)1.

A common single nucleotide polymorphism can exacerbate long-QT type 2 syndrome leading to sudden infant death.

Background: Identification of infants at risk for sudden arrhythmic death remains one of the leading challenges of modern medicine. We present a family in which a common polymorphism (single nucleotide polymorphism) inherited from the father, combined with a stop codon mutation inherited from the mother (both asymptomatic), led to 2 cases of sudden infant death.

Methods And Results: KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, CACNA1c, CACNB2b, and KCNJ2 genes were amplified and analyzed by direct sequencing.

A mutation in the beta 3 subunit of the cardiac sodium channel associated with Brugada ECG phenotype.

Background: Brugada syndrome, characterized by ST-segment elevation in the right precordial ECG leads and the development of life-threatening ventricular arrhythmias, has been associated with mutations in 6 different genes. We identify and characterize a mutation in a new gene.

Methods And Results: A 64-year-old white male displayed a type 1 ST-segment elevation in V1 and V2 during procainamide challenge.

Dual variation in SCN5A and CACNB2b underlies the development of cardiac conduction disease without Brugada syndrome.

Background: Inherited loss of function mutations in SCN5A have been linked to overlapping syndromes including cardiac conduction disease and Brugada syndrome (BrS). The mechanisms responsible for the development of one without the other are poorly understood.

Methods: Direct sequencing was performed in a family with cardiac conduction disease.

Accelerated inactivation of the L-type calcium current due to a mutation in CACNB2b underlies Brugada syndrome.

Recent studies have demonstrated an association between mutations in CACNA1c or CACNB2b and Brugada syndrome (BrS). Previously described mutations all caused a loss of function secondary to a reduction of peak calcium current (I(Ca)). We describe a novel CACNB2b mutation associated with BrS in which loss of function is caused by accelerated inactivation of I(Ca).

SCN5A mutation associated with acute myocardial infarction.

Ventricular tachycardia and fibrillation (VT/VF) complicating Brugada syndrome, a genetic disorder linked to SCN5A mutations, and VF complicating acute myocardial infarction (AMI) have both been linked to phase 2 reentry. Because of these mechanistic similarities in arrhythmogenesis, we examined the contribution of SCN5A mutations to VT/VF complicating AMI. Nineteen consecutive patients developing VF during AMI were enrolled.

Functional effects of KCNE3 mutation and its role in the development of Brugada syndrome.

Introduction: The Brugada Syndrome (BrS), an inherited syndrome associated with a high incidence of sudden cardiac arrest, has been linked to mutations in four different genes leading to a loss of function in sodium and calcium channel activity. Although the transient outward current (I(to)) is thought to play a prominent role in the expression of the syndrome, mutations in I(to)-related genes have not been identified as yet.

Methods And Results: One hundred and five probands with BrS were screened for ion channel gene mutations using single strand conformation polymorphism (SSCP) electrophoresis and direct sequencing.

Lidocaine-induced Brugada syndrome phenotype linked to a novel double mutation in the cardiac sodium channel.

Brugada syndrome has been linked to mutations in SCN5A. Agents that dissociate slowly from the sodium channel such as flecainide and ajmaline unmask the Brugada syndrome electrocardiogram and precipitate ventricular tachycardia/fibrillation. Lidocaine, an agent with rapid dissociation kinetics, has previously been shown to exert no effect in patients with Brugada syndrome.

Gain of function in IKs secondary to a mutation in KCNE5 associated with atrial fibrillation.

Background: Atrial fibrillation (AF) is the most common clinical arrhythmia and a major cause of cardiovascular morbidity and mortality. Among the gene defects previously associated with AF is a gain of function of the slowly activating delayed rectifier potassium current IKs, secondary to mutations in KCNQ1. Coexpression of KCNE5, the gene encoding the MiRP4 beta-subunit, has been shown to reduce IKs.

Novel mutation in the SCN5A gene associated with arrhythmic storm development during acute myocardial infarction.

Background: Ventricular tachycardia (VT) and ventricular fibrillation (VF) complicating Brugada syndrome, a genetic disorder linked to SCN5A mutations, and VF complicating acute myocardial infarction (AMI) both have been linked to phase 2 reentry.

Objective: Given the mechanistic similarities in arrhythmogenesis, the purpose of this study was to examine the contribution of SCN5A mutations to VT/VF complicating AMI.

Methods: Nineteen consecutive patients developing VF during AMI were enrolled in the study.

Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death.

Background: Cardiac ion channelopathies are responsible for an ever-increasing number and diversity of familial cardiac arrhythmia syndromes. We describe a new clinical entity that consists of an ST-segment elevation in the right precordial ECG leads, a shorter-than-normal QT interval, and a history of sudden cardiac death.

Methods And Results: Eighty-two consecutive probands with Brugada syndrome were screened for ion channel gene mutations with direct sequencing.

Compound heterozygous mutations P336L and I1660V in the human cardiac sodium channel associated with the Brugada syndrome.

Background: Loss-of-function mutations in SCN5A have been associated with the Brugada syndrome. We report the first Brugada syndrome family with compound heterozygous mutations in SCN5A. The proband inherited 1 mutation from each parent and transmitted 1 to each daughter.

Genetic and biophysical basis for bupivacaine-induced ST segment elevation and VT/VF. Anesthesia unmasked Brugada syndrome.

Background: Brugada syndrome is an inherited disease associated with sudden cardiac death. The electrocardiographic pattern associated with Brugada syndrome has been linked to the use of sodium channel blockers, including antiarrhythmics, trycyclics and anesthetics.

Objective: We report a case of bupivacaine-induced Brugada syndrome, in which we investigated the genetic, biophysical and path physiological mechanism involved.

De novo KCNQ1 mutation responsible for atrial fibrillation and short QT syndrome in utero.

Objective: We describe a genetic basis for atrial fibrillation and short QT syndrome in utero. Heterologous expression of the mutant channel was used to define the physiological consequences of the mutation.

Methods: A baby girl was born at 38 weeks after induction of delivery that was prompted by bradycardia and irregular rythm.