Congenital Long QT Syndrome Research Articles

Prolonged QTc interval is a powerful predictor of non-cardiac mortality in patients with aneurysmal subarachnoid hemorrhage independently of traditional risk factors

Prolonged QTc interval is a powerful predictor of non-cardiac mortality in patients with aneurysmal subarachnoid hemorrhage independently of traditional risk factors

To Be or Not to Be

Congenital long-QT syndrome (LQTS) is a rare heritable disorder that is associated with a high risk of syncope and sudden cardiac death. Since 1996, LQTS has been categorized based on mutations to genes that encode cardiac ion channel subunits or proteins that modulate ionic currents in the heart. The most common LQTS gene mutations involve KCNQ1 (LQT1), KCNH2 (LQT2), and SCN5A (LQT3). Multiple other rare gene mutations have been identified and postulated to cause LQTS (LQT4–LQT13). However, in some cases, the identified mutations are part of a more complex clinical disorder (ie, LQT7 and LQT8) and may not be part of the LQTS in the classical sense. In other cases, such as LQT9, there are limited data supporting a causative link between a mutation and LQTS. Article see p 452 The CAV3 gene encodes an integral membrane protein called caveolin 3. Caveolins play an important role in signal transduction and vesicular transport within cells. Mutations to CAV3 have been found to cause diseases of both skeletal and cardiac muscle. Furthermore, mutations to CAV3 were recently identified as rare, potentially disease-causing mutations in a series of patients referred for LQTS genetic testing.1 In 2006, Vatta et al1 reported finding 1 of 4 novel CAV3 mutations (T78M, A85T, F97C, and S141R) in 6 (0.7%) of 904 unrelated patients. Cellular electrophysiological characterization of 2 of these mutations (F97C and S141R) revealed that the mutations resulted in as much as a 4-fold increase in the late sodium current (INaL). Based on the recognition that …

Response of QT interval in methadone maintenance treated patients to the rapid changes in heart rate provoked by brisk standing: Comparison to healthy controls and patients with long QT syndrome

BackgroundPatients on methadone maintenance therapy are somehow similar to patients with congenital long QT syndrome (LQTS) because they have malfunction of potassium channels caused by a drug that cannot be easily discontinued. We tested patients on methadone therapy with the “stand-up” test, which has been shown to unravel pathologic QT-prolongation in congenital long-QT patients. Methods“Stand-up” test results of methadone-users, healthy volunteers and congenital LQTS patients were compared. Methadone serum levels and doses were collected. The prognostic value of the test was evaluated after 4years of follow-up. ResultsThe QT-response of methadone-users to the “stand-up” test resembled that of healthy volunteers more than the response of LQTS-patients. Differences in the QTc of methadone treated patients and controls, which were statistically significant at baseline, became no longer significant after standing. Within 52months of follow-up, one patient had suffered unexplained death and one had documented ventricular tachycardia. ConclusionsThe QT-response of methadone-users to the “stand-up” test is similar to that of healthy volunteers, not to that of LQTS-patients.

A novel deletion-frameshift mutation in the S1 region of HERG gene in a Chinese family with long QT syndrome

Background The congenital Long QT syndrome (LQTS) is a hereditary cardiac channelopathy that is characterized by a prolonged QT interval, syncope, ventricular arrhythmias, and sudden death. The chromosome 7-linked type 2 congenital LQTS (LQT2) is caused by gene mutations in the human ether-a-go-go-related gene (HERG). Methods A Chinese family diagnosed with LQTS were screened for KCNQ1, HERG and SCN5A, using polymerase chain reaction (PCR), direct sequencing, and clong sequencing. We also investigated the mRNA expression of the HERG gene. Results We identified a novel I414fs+98X mutation in the HERG gene. The deletion mutation of 14-bp in the first transmembrane segment (S1) introduced premature termination codons (PTCs) at the end of exon 6. This mutation would result in a serious phenotype if the truncated proteins co-assembled with normal subunit to form the defective channels. But only the proband was symptomatic. Conclusions We found that the mRNA level of the HERG gene was significantly lower in I414fs+98X carriers than in noncarriers. We found a novel I414fs+98X mutation. The mRNA level supports that NMD mechanism might regulate the novel mutation.

Arrhythmia Risk in Long QT Syndrome

Congenital long QT syndrome (LQTS) is a genetically heterogeneous disorder of myocardial repolarization that affects an estimated 1:2000 individuals and often manifests clinically as a prolonged heart rate–corrected QT interval (QTc) on ECG and as an increased proclivity for torsadogenic-mediated syncope, seizures, and sudden death.1 From a genetic perspective, LQTS has been considered classically an autosomal dominant genetic disorder, with heterozygous mutations in the 3 major LQTS-susceptibility genes accounting for ≈75% of clinically robust, nonsyndromic LQTS cases ( KCNQ1 /LQT1, 30%–35%; KCNH2 /LQT2, 25%–30%, and SCN5A /LQT3, 5%–10%).2,3 However, since the identification of the 3 major LQTS-susceptibility genes in 1995 and 1996, it has become clear that LQTS, like many other monogenic/Mendelian disorders, is at best described as an autosomal dominant disorder with marked incomplete penetrance and variable expressivity whereby related individuals who harbor the same LQTS-causative mutation often assume vastly different clinical courses in terms of QTc duration and frequency of cardiac events.4 Article see p 354 In retrospect, strong evidence for this extensive phenotypic variability in LQTS was encountered long before the specific ion channel genes were implicated in the pathogenesis of the disorder. In 1992, 4 years before KCNQ1 was identified as the culprit, LQT1-causative gene residing within the chromosome 11p15.5 genetic locus, Vincent et al5 described both a significant overlap in the range of QTc values between 11p15.5 locus carriers (410–590 ms; mean, 490 ms) and noncarriers (380–470 ms; mean, 420 ms) and marked variability in the frequency and severity of cardiac events between carriers of the same 11p genetic marker (63% with syncope; 5% with sudden cardiac arrest).4 Subsequent studies, including those involving large founder populations such as the South African KCNQ1-A341V LQT1 kindred, went on to demonstrate that few LQTS-causative mutations completely escape the genetic phenomena of incomplete …

Foetal presentation of long QT syndrome

Summary Long-QT syndrome is a rare, inherited cardiac channelopathy that is characterized by arrhythmia, syncope and sudden cardiac death. Foetal symptoms are very rare and prenatal diagnosis is diffi cult. We report on a foetal presentation of long-QT syndrome with severe hydrops and a chaotic heart rhythm at 32 weeks of gestation. Postnatal electrocardiography showed runs of polymorphic ventricular tachycardia and an extremely prolonged-QT segment (QTc of 640 ms). The initial approach of overdrive pacing, followed by the combined therapy of a beta blocker, a sodium channel blocker (mexiletine) and potassium suppletion proved successful in maintaining a stable sinus rhythm. The girl was doing well at eight months of followup. In this patient a timely diagnosis and eff ective management after birth have been life-saving. The intrauterine manifestation of foetal atrioventricular dissociation and ventricular arrhythmia should raise suspicion of congenital long-QT syndrome.

Non dominant-negative KCNJ2 gene mutations leading to Andersen-Tawil syndrome with an isolated cardiac phenotype

Andersen-Tawil syndrome (ATS) is characterized by dysmorphic features, periodic paralyses and abnormal ventricular repolarization. After genotyping a large set of patients with congenital long-QT syndrome, we identified two novel, heterozygous KCNJ2 mutations (p.N318S, p.W322C) located in the C-terminus of the Kir2.1 subunit. These mutations have a different localization than classical ATS mutations which are mostly located at a potential interaction face with the slide helix or at the interface between the C-termini. Mutation carriers were without the key features of ATS, causing an isolated cardiac phenotype. While the N318S mutants regularly reached the plasma membrane, W322C mutants primarily resided in late endosomes. Co-expression of N318S or W322C with wild-type Kir2.1 reduced current amplitudes only by 20-25%. This mild loss-of-function for the heteromeric channels resulted from defective channel trafficking (W322C) or gating (N318S). Strikingly, and in contrast to the majority of ATS mutations, neither mutant caused a dominant-negative suppression of wild-type Kir2.1, Kir2.2 and Kir2.3 currents. Thus, a mild reduction of native Kir2.x currents by non dominant-negative mutants may cause ATS with an isolated cardiac phenotype.

Safety and effectiveness of drug therapy for the acutely agitated patient (Part I)

Acute agitation occurs in a variety of medical and psychiatric conditions, and the management of agitated, abusive, or violent patients is a common problem in the emergency department. Rapid control of potentially dangerous behaviors by physical restraint and pharmacologic tranquillization is crucial to ensure the safety of the patient and health-care personnel and to allow diagnostic procedures and treatment of the underlying condition. The purpose of this article (the first in a 2-part series) is to review the extensive safety data published on the antipsychotic medications currently available for managing situations of this type, including older neuroleptics like haloperidol, chlorpromazine, and pimozide as well as a number of the newer atypical antipsychotics (olanzapine, risperidone, ziprasidone). Particular attention is focused on the ability of these drugs to lengthen the QT interval in surface electrocardiograms. This adverse effect is of major concern, especially in light of the reported relation between QT interval and the risk of sudden death. In patients with the congenital long-QT syndrome, a long QT interval is associated with a fatal paroxysmal ventricular arrhythmia knownas torsades de pointes. Therefore, careful evaluation of the QT-prolonging properties and arrhythmogenic potential of antipsychotic drugs is urgently needed. Clinical assessment of drug-induced QT-interval prolongation is strictly dependent on the quality of electrocardiographic data and the appropriateness of electrocardiographic analyses. Unfortunately, measurement imprecision and natural variability preclude a simple use of the actually measured QT interval as a surrogate marker of drug-induced proarrhythmia. Because the QT interval changes with heart rate, a rate-corrected QT interval (QTc) is commonly used when evaluating a drug’s effect. In clinical settings, themost widely used formulas for rate-correction are those of Bazett (QTc=QT/RR^0.5) and Fridericia (QTc=QT/RR^0.33), both of which standardize themeasuredQTinterval to an RRinterval of 1 s (heart rate of 60 bpm).However, QT variability can also be influenced by other factors that are more difficult to measure, including body fat, meals, psycho-physical distress, and circadian and seasonal fluctuations.

Genetics of congenital and drug-induced long QT syndromes: current evidence and future research perspectives

The long QT syndrome (LQTS) is a condition characterized by abnormal prolongation of the QT interval with an associated risk of ventricular arrhythmias and sudden cardiac death. Congenital forms of LQTS arise due to rare and highly penetrant mutations that segregate in a Mendelian fashion. Over the years, multiple mutations in genes encoding ion channels and ion channel binding proteins have been reported to underlie congenital LQTS. Drugs are by far the most common cause of acquired forms of LQTS. Emerging evidence suggests that drug-induced LQTS also has a significant heritable component. However, the genetic substrate underlying drug-induced LQTS is presently largely unknown. In recent years, advances in next-generation sequencing technology and molecular biology techniques have significantly enhanced our ability to identify genetic variants underlying both monogenic diseases and more complex traits. In this review, we discuss the genetic basis of congenital and drug-induced LQTS and focus on future avenues of research in the field. Ultimately, a detailed characterization of the genetic substrate underlying congenital and drug-induced LQTS will enhance risk stratification and potentially result in the development of tailored genotype-based therapies.

SCN5A Mutation Positivity in a Patient with Juvenile Myoclonic Epilepsy and Congenital Long-QT Syndrome Type 3 (P05.090)

SCN5A Mutation Positivity in a Patient with Juvenile Myoclonic Epilepsy and Congenital Long-QT Syndrome Type 3 (P05.090)

Calmodulin Mutations Associated With Recurrent Cardiac Arrest in Infants

Life-threatening disorders of heart rhythm may arise during infancy and can result in the sudden and tragic death of a child. We performed exome sequencing on 2 unrelated infants presenting with recurrent cardiac arrest to discover a genetic cause. We ascertained 2 unrelated infants (probands) with recurrent cardiac arrest and dramatically prolonged QTc interval who were both born to healthy parents. The 2 parent-child trios were investigated with the use of exome sequencing to search for de novo genetic variants. We then performed follow-up candidate gene screening on an independent cohort of 82 subjects with congenital long-QT syndrome without an identified genetic cause. Biochemical studies were performed to determine the functional consequences of mutations discovered in 2 genes encoding calmodulin. We discovered 3 heterozygous de novo mutations in either CALM1 or CALM2, 2 of the 3 human genes encoding calmodulin, in the 2 probands and in 2 additional subjects with recurrent cardiac arrest. All mutation carriers were infants who exhibited life-threatening ventricular arrhythmias combined variably with epilepsy and delayed neurodevelopment. Mutations altered residues in or adjacent to critical calcium binding loops in the calmodulin carboxyl-terminal domain. Recombinant mutant calmodulins exhibited several-fold reductions in calcium binding affinity. Human calmodulin mutations disrupt calcium ion binding to the protein and are associated with a life-threatening condition in early infancy. Defects in calmodulin function will disrupt important calcium signaling events in heart, affecting membrane ion channels, a plausible molecular mechanism for potentially deadly disturbances in heart rhythm during infancy.

Prognostic implications of mutation-specific QTc standard deviation in congenital long QT syndrome.

Individual corrected QT interval (QTc) may vary widely among carriers of the same long QT syndrome (LQTS) mutation. Currently, neither the mechanism nor the implications of this variable penetrance are well understood. To hypothesize that the assessment of QTc variance in patients with congenital LQTS who carry the same mutation provides incremental prognostic information on the patient-specific QTc. The study population comprised 1206 patients with LQTS with 95 different mutations and ≥ 5 individuals who carry the same mutation. Multivariate Cox proportional hazards regression analysis was used to assess the effect of mutation-specific standard deviation of QTc (QTcSD) on the risk of cardiac events (comprising syncope, aborted cardiac arrest, and sudden cardiac death) from birth through age 40 years in the total population and by genotype. Assessment of mutation-specific QTcSD showed large differences among carriers of the same mutations (median QTcSD 45 ms). Multivariate analysis showed that each 20 ms increment in QTcSD was associated with a significant 33% (P = .002) increase in the risk of cardiac events after adjustment for the patient-specific QTc duration and the family effect on QTc. The risk associated with QTcSD was pronounced among patients with long QT syndrome type 1 (hazard ratio 1.55 per 20 ms increment; P<.001), whereas among patients with long QT syndrome type 2, the risk associated with QTcSD was not statistically significant (hazard ratio 0.99; P = .95; P value for QTcSD-by-genotype interaction = .002). Our findings suggest that mutations with a wider variation in QTc duration are associated with increased risk of cardiac events. These findings appear to be genotype-specific, with a pronounced effect among patients with the long QT syndrome type 1 genotype.

Torsade de Pointes Associated With Laxative Abuse in a Patient Receiving Methadone

Back to table of contents Previous article Next article LettersFull AccessTorsade de Pointes Associated With Laxative Abuse in a Patient Receiving MethadoneXavier Laqueille, M.D., Christophe Genin, M.D., Benjamin Pitrat, M.D., Aline Lupuyau, M.D., and Alain Dervaux, M.D., Ph.D.Xavier LaqueilleSearch for more papers by this author, M.D., Christophe GeninSearch for more papers by this author, M.D., Benjamin PitratSearch for more papers by this author, M.D., Aline LupuyauSearch for more papers by this author, M.D., and Alain DervauxSearch for more papers by this author, M.D., Ph.D.Published Online:1 Oct 2013https://doi.org/10.1176/appi.neuropsych.12090224AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: The risk factors of torsade de pointes are: drug-induced Q-Tc prolongation, female gender, hypokalemia, unrecognized congenital long Q-T syndrome (LQTS), and predisposing DNA polymorphisms.1,2 These risk factors have not been studied in patients receiving methadone, a drug associated with Q-Tc interval prolongation, with a dose–effect relationship.2,3 Also, drug-induced Q-Tc prolongation can be a potentially dangerous adverse effect of medication combinations. Most of the torsade de pointes caused by polypharmacy, including methadone, were reported in patients with human immunodeficiency virus (HIV). We report the case of a patient on stable methadone treatment, without HIV infection, whose condition suddenly worsened with hidden laxative abuse.Case Report“Ms. A,” a 46-year-old, white woman, had a history of cocaine and heroin dependence (discontinued 2 years ago, with negative urinary drug analysis) and cannabis dependence. She received methadone maintenance treatment, 80–200 mg/day for 4 years. The ECG recorded 3 months before the emergency department presentation was normal: Q-Tc 396 msec.During her hospitalization to reduce methadone doses, while she received methadone 200 mg/day, the patient presented sudden death and was resuscitated after an episode of torsade de pointes. In the emergency department, the initial ECG on presentation showed ventricular tachycardia with torsade de pointes and Q-Tc 491 msec. The torsade de pointes resolved spontaneously. In the cardiac intensive care unit, she developed another episode of torsade de pointes. During hospitalization in the cardiology department, repetition of the ECG showed increased Q-Tc of 500 msec. The echocardiography found a left ventricular dysfunction (left ventricular ejection fraction: 20%−25%). Laboratory testing revealed hypokalemia (2.7 mmol/l). A treatment including ramipril and bisoprolol was started, and the patient’s condition improved. An empty box of laxatives (bisacodyl) was found in the patient's room. The patient acknowledged taking laxative to lose weight. She fulfilled DSM-IV-TR criteria for eating disorder, NOS.DiscussionThe cause of torsade de pointes is generally multifactorial. Our patient presented several risk factors for torsade de pointes: 1) female gender; 2) high doses of methadone; and 3) severe hypokalemia induced by hidden laxative abuse. Also, since the patient’s maternal grandmother died from sudden death, a congenital LQTS cannot be excluded.This case highlights the need for carefully monitoring patients treated with methadone for potentially dangerous Q-T prolongation, which can occur even after the patients have been on therapy for some time. Patients should be informed that laxative use/abuse could lead to hypokalemia and increase their risk of developing a prolonged Q-T interval.3 ECG should be repeated to look for Q-Tc prolongation, but that may not be sufficient. Clinical investigations and ionograms could help to detect surreptitious laxative abuse.Service d’Addictologie du Centre Hospitalier Sainte-AnneParis, FranceService d’Addictologie de la Polyclinique La ConcordeAlfortville, FranceCorrespondence: Dr Alain Dervaux; e-mail: a.[email protected]frConflict of interest: Alain Dervaux has received honoraria for lectures from Bristol-Myers Squibb, Lundbeck, and Lilly. The other authors declare no conflicts of interest.References1 Sauer AJ, Newton-Cheh C: Clinical and genetic determinants of torsade de pointes risk. Circulation 2012; 125:1684–1694Crossref, Medline, Google Scholar2 Stringer J, Welsh C, Tommasello A: Methadone-associated Q-T interval prolongation and torsades de pointes. Am J Health Syst Pharm 2009; 66:825–833Crossref, Medline, Google Scholar3 Krantz MJ, Martin J, Stimmel B, et al.: Q-Tc interval screening in methadone treatment. Ann Intern Med 2009; 150:387–395Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited ByAdverse drug event of hypokalaemia‐induced cardiotoxicity secondary to the use of laxatives: A systematic review of case reports16 July 2020 | Journal of Clinical Pharmacy and Therapeutics, Vol. 2La pratique clinique des traitements de substitution à l’héroïne et les alternativesBulletin de l'Académie Nationale de Médecine, Vol. 200, No. 4-5Bisacodyl/methadone6 September 2014 | Reactions Weekly, Vol. 1517, No. 1 Volume 25Issue 4 Fall 2013Pages E24-E24 Metrics PDF download History Published online 1 October 2013 Published in print 1 October 2013

Long QT Syndrome: a Korean Single Center Study

The long QT syndrome (LQTS) is a rare hereditary disorder in which affected individuals have a possibility of ventricular tachyarrhythmia and sudden cardiac death. We investigated 62 LQTS (QTc ≥ 0.47 sec) and 19 family members whose genetic study revealed mutation of LQT gene. In the proband group, the modes of presentation were ECG abnormality (38.7%), aborted cardiac arrest (24.2%), and syncope or seizure (19.4%). Median age of initial symptom development was 10.5 yr. Genetic studies were performed in 61; and mutations were found in 40 cases (KCNQ1 in 19, KCNH2 in 10, SCN5A in 7, KCNJ2 in 3, and CACNA1C in 1). In the family group, the penetrance of LQT gene mutation was 57.9%. QTc was longer as patients had the history of syncope (P = 0.001), ventricular tachycardia (P = 0.017) and aborted arrest (P = 0.010). QTc longer than 0.508 sec could be a cut-off value for major cardiac events (sensitivity 0.806, specificity 0.600). Beta-blocker was frequently applied for treatment and had significant effects on reducing QTc (P = 0.007). Implantable cardioverter defibrillators were applied in 6 patients. Congenital LQTS is a potentially lethal disease. It shows various genetic mutations with low penetrance in Korean patients.

Update of Diagnosis and Management of Inherited Cardiac Arrhythmias

Over the past 2 decades, a number of inherited cardiac arrhythmias, including congenital long QT syndrome (LQTS) and Brugada syndrome (BrS), have been shown to have a link to mutations in genes encoding for ion channels or other membrane components. The recent HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited arrhythmia syndromes has updated the clinical diagnosis of congenital LQTS and BrS. Genetic studies have identified 13 forms of congenital LQTS in 50-80% of clinically affected patients. Genotype-phenotype correlations have been investigated in the 3 major genotypes, LQT1, LQT2 and LQT3 syndromes, resulting in genotype-specific management and therapy. More detailed analyses of each genotype have suggested mutation location-, type-, or function-specific differences in clinical phenotype among the LQT1, LQT2, and possibly LQT3 genotypes. In BrS, only one-third of affected patients can be genotyped, mainly in the sodium channel gene, SCN5A; therefore, clinical studies of genotype-phenotype relationships have been limited. More recently, a genome-wide association study using a gene array explored the role of common genetic variants (polymorphisms) as the susceptible or modifier gene in both congenital LQTS and BrS.

Gene mutations in cardiac arrhythmias: a review of recent evidence in ion channelopathies

Over the past 15 years, molecular genetic studies have linked gene mutations to many inherited arrhythmogenic disorders, in particular, “ion channelopathies”, in which mutations in genes encode functional units of ion channels and/or their transporter-associated proteins in patients without primary cardiac structural abnormalities. These disorders are exemplified by congenital long QT syndrome (LQTS), short QT syndrome, Brugada syndrome (BrS) and catecholaminergic polymorphic ventricular tachycardia (CPVT). Functional and pathophysiological studies have led to better understanding of the clinical spectrum, ion channel structures and cellular electrophysiology involving dynamics of intracellular calcium cycling in many subtypes of these disorders and more importantly, development of potentially more effective pharmacological agents and even curative gene therapy. In this review, we have summarized (1) the significance of unveiling mutations in genes encoding transporter-associated proteins as the cause of congenital LQTS, (2) the technique of catheter ablation applied at the right ventricular outflow tract may be curative for severely symptomatic BrS, (3) mutations with channel function modulated by protein Kinase A-dependent phosphorylation can be the culprit of CPVT mimicry in Andersen-Tawil syndrome (LQT7), (4) ablation of the ion channel anchoring protein may prevent arrhythmogenesis in Timothy syndrome (LQT8), (5) altered intracellular Ca2+ cycling can be the basis of effective targeted pharmacotherapy in CPVT, and (6) the technology of induced pluripotent stem cells is a promising diagnostic and research tool as it has become a new paradigm for pathophysiological study of patient- and disease-specific cells aimed at screening new drugs and eventual clinical application of gene therapy. Lastly, we have discussed (7) genotype-phenotype correlation in relation to risk stratification of patients with congenital LQTS in clinical practice.

Torsades de pointes observed in the early postoperative period in a patient with long QT syndrome

Torsades de pointes observed in the early postoperative period in a patient with long QT syndrome

Quantitative PCR as an alternative in the diagnosis of long-QT syndrome.

Congenital long-QT syndrome is a genetic disorder associated with abnormalities in the function and/or structure of cardiac ion channels. Up to the present, 13 types of the disease have been described (LQTS1-13) which result from the fact that 13 genes of which mutations can have an influence on the occurrence of the disease have been identified. Characteristic symptoms of the disease include the changes in the ECG (QT interval prolonged above 450 ms), “torsade de pointes,” fainting, and even sudden cardiac death. The present study has been focused on two types of the disease, namely, LQTS1 and LQTS2. The examination of two appropriate genes expression (KCNQ1; KCNH2) at the transcription level by QRT-PCR in a group of LQTS patients and a healthy control group showed different transcriptional activities of KCNH2 gene in LQTS2 patients compared to the control individuals. KCNQ1 gene expression study did not reveal such differences between both groups. The results indicate that QRT-PCR may serve as a complimentary method to the identification of molecular alterations in genetic determinants of LQTS2 only, but it cannot be used as a sole diagnostic criterion.

Repeated Aborted Sudden Cardiac Death with Long QT Syndrome in a Patient with Anomalous Origin of the Right Coronary Artery from the Left Coronary Cusp

A 15-year-old female with a prior history of aborted cardiac death and surgical correction of anomalous origin of the right coronary artery (RCA) presented with polymorphic ventricular tachycardia. Her electrocardiogram after defibrillation was suggestive of congenital long QT syndrome (LQTS). The patient was treated with a β-blocker and remained free from ventricular arrhythmia during the follow-up of more than 6 months. Here, we present the case of a young female with repeated aborted cardiac death accompanied by anomalous origin of the RCA and congenital LQTS for the first time.

Probing the Membrane Bound KCNE1 Protein with Solid State NMR Spectroscopy

KCNE1, also known as MinK, is a membrane protein that associates with the KCNQ1 channel protein to form a voltage-gated potassium channel. This ion channel is essential to the cardiac action potential that mediates heartbeat and is also critical for potassium ion homeostasis in the inner ear. Dominant mutations in KCNE1 lead to congenital long-QT syndrome and congenital deafness. KCNE1 has been over expressed in E. coli, purified into micelles using his-tag affinity chromatography, and reconstituted into POPC/POPG vesicles. 31P NMR powder spectra results confirm vesicle formation. Different KCNE1 mutants have been labeled using MTSL, one mutant outside the membrane and the other inside the membrane. By measuring 31P relaxation times of the lipids, we can determine the depth that at which KCNE1 is buried inside the vesicles. We also introduced a bicelle system to study the topology of uniform 15N labeled KCNE1 with respect to the lipid bilayer. By measuring the 15N NMR signal, we are able to figure out the structural topology of KCNE1 within the lipid bilayer.