Disease relevance of Long QT Syndrome

• In this study, we describe two new loci for an inherited cardiac arrhythmia, long QT syndrome (LQT) [1].
• We screened genomic DNA from a child who died of SIDS and identified a de-novo mutation in KVLQT1, the gene most frequently associated with long QT syndrome [2].
• The most common problem is acquired long QT syndrome caused by drugs that block human ether-a-go-go-related-gene (hERG) K(+) channels, delay cardiac repolarization and increase the risk of torsades de pointes arrhythmia (TdP) [3].
• BACKGROUND: Mutations in the gene encoding the human cardiac Na(+) channel alpha-subunit (hH1) are responsible for chromosome 3-linked congenital long-QT syndrome (LQT3) and idiopathic ventricular fibrillation (IVF) [4].
• The long-QT syndrome (LQT; Ward-Romano syndrome) is a cardiac disorder that is inherited as an autosomal dominant trait [5].

Psychiatry related information on Long QT Syndrome

• OBJECTIVE: Patients with HERG-associated long QT syndrome typically develop tachyarrhythmias during physical or emotional stress [6].

High impact information on Long QT Syndrome

• METHODS: We determined the genotypes of 541 of 1378 members of 38 families enrolled in the International Long-QT Syndrome Registry: 112 had mutations at the LQT1 locus, 72 had mutations at the LQT2 locus, and 62 had mutations at the LQT3 locus [7].
• Because KVLQT1 mutations cause arrhythmia susceptibility in the long QT syndrome (LQT), we hypothesized that mutations in KCNE1 also cause this disorder [8].
• Recombinants allowed us to map the JLN gene between D11S922 and D11S4146, to a 6-cM interval where KVLQT1, a potassium channel gene causing Romano-Ward (RW) syndrome, the dominant form of long QT syndrome, has been previously localized [9].
• Images in clinical medicine. Congenital long-QT syndrome [10].
• Deletion of amino-acid residues 1505-1507 (KPQ) in the cardiac SCN5A Na(+) channel causes autosomal dominant prolongation of the electrocardiographic QT interval (long-QT syndrome type 3 or LQT3) [11].

Chemical compound and disease context of Long QT Syndrome

• We have identified a four-generation family, including 17 gene carriers with long QT syndrome, Brugada syndrome, and conduction system disease with deletion of lysine 1500 (DeltaK1500) within the linker [12].
• Primidone in the treatment of the long QT syndrome: QT shortening and ventricular arrhythmia suppression [13].
• Sodium channel block with mexiletine is effective in reducing dispersion of repolarization and preventing torsade des pointes in LQT2 and LQT3 models of the long-QT syndrome [14].
• Early afterdepolarizations induced by isoproterenol in patients with congenital long QT syndrome [15].
• Electrophysiological mechanisms in a canine model of erythromycin-associated long QT syndrome [16].

Biological context of Long QT Syndrome

• KVLQT1 C-terminal missense mutation causes a forme fruste long-QT syndrome [17].
• Here we report the identification of eight unrelated probands harboring ankyrin-B loss-of-function mutations, including four previously undescribed mutations, whose clinical features distinguish the cardiac phenotype associated with loss of ankyrin-B activity from classic long QT syndromes [18].
• Amino acid sequence comparison reveals that both genes share strong homology to KvLQT1, the potassium channel encoded by KCNQ1, which is responsible for over 50% of inherited long QT syndrome [19].
• This study used monophasic action potentials to investigate the effects of verapamil and propranolol on epinephrine-induced repolarization abnormalities in congenital long QT syndrome [20].
• Molecular genetics of the long QT syndrome: two novel mutations of the KVLQT1 gene and phenotypic expression of the mutant gene in a large kindred [21].

Anatomical context of Long QT Syndrome

• Expression of the erg1 gene in the sympathetic nervous system has potential implications for the etiology of the LQT2 form of the human genetic disease long QT syndrome [22].
• A cellular model for long QT syndrome. Trapping of heteromultimeric complexes consisting of truncated Kv1.1 potassium channel polypeptides and native Kv1.4 and Kv1.5 channels in the endoplasmic reticulum [23].
• Sinus node function and ventricular repolarization during exercise stress test in long QT syndrome patients with KvLQT1 and HERG potassium channel defects [24].
• In isolated myocytes I(Kr) frequently is small in amplitude or absent, yet KCNH2 channels and I(Kr) are targets for drug block or mutations to cause long QT syndrome [25].
• Underlying cardiac abnormalities consisted most commonly of cardiomyopathy (nine), long QT syndrome (LQTS) (five), and mitral valve prolapse (five); no identifiable heart disease was found in four patients [26].

Gene context of Long QT Syndrome

• RESULTS: We identified KCNQ1, which is mutated in cardiac long QT syndrome, as a K+ channel located in tubulovesicles and apical membrane of parietal cells, where it colocalized with H+/K+-adenosine triphosphatase [27].
• Identification of a new SCN5A mutation, D1840G, associated with the long QT syndrome. Mutations in brief no. 153. Online [28].
• CONCLUSION: The data suggest that mutations in KCND2 and KCND3 are not a frequent cause of long QT syndrome [29].
• BACKGROUND: Mutations in KCNE2 have been linked to long-QT syndrome (LQT6), yet KCNE2 protein expression in the ventricle and its functional role in native channels are not clear [30].
• Targeted mutational analysis of ankyrin-B in 541 consecutive, unrelated patients referred for long QT syndrome genetic testing and 200 healthy subjects [31].

Analytical, diagnostic and therapeutic context of Long QT Syndrome

• Mutation site-specific differences in arrhythmic risk and sensitivity to sympathetic stimulation in the LQT1 form of congenital long QT syndrome: multicenter study in Japan [32].
• Incidence and clinical features of the quinidine-associated long QT syndrome: implications for patient care [33].
• Standard therapies for long-QT syndrome include correction of the underlying cause, alleviation of the precipitating factors, magnesium sulfate, isoproterenol, antiadrenergic therapy (beta-adrenergic receptor blockers, left cervicothoracic sympathectomy), cardiac pacing, and implantable cardioverter defibrillator [34].
• Since May 2004, genetic testing has been available as a clinical diagnostic test for both hypertrophic cardiomyopathy and long QT syndrome [35].
• Prevention of class III-induced proarrhythmias by flecainide in an animal model of the acquired long QT syndrome [36].

References