Pre-Test Probability and Genes and Variants of Uncertain Significance in Familial Long QT Syndrome

The genetics underlying familial long QT syndrome (LQTS) are among the best characterised of all of the inherited heart conditions. Cohort and registry studies have demonstrated important genotype-phenotype correlations that are now essential in guiding clinical practice of patients with the most common three genotypes; KCNQ1 (LQT type 1), KCNH2 (LQT type 2) and SCN5A (LQT type 3). However, the growing number of genes —now more than 16—is confusing, and there is much doubt as to whether many actually cause LQTS at all.
Source: Heart, Lung and Circulation - Category: Cardiology Authors: Source Type: research

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The human ether-á-go-go–related gene (hERG1) channel conducts small outward K+ currents that are critical for cardiomyocyte membrane repolarization. The gain-of-function mutation N629D at the outer mouth of the selectivity filter (SF) disrupts inactivation and K+-selective transport in hERG1, leading to arrhythmogenic phenotypes associated with long-QT syndrome. Here, we combined computational...
Source: Proceedings of the National Academy of Sciences - Category: Science Authors: Tags: PNAS Plus Source Type: research
KCNE1 loss-of-function variants cause type 5 long QT syndrome (LQT5). However, most alleged LQT5-causative KCNE1 variants were identified before the true rate of background genetic variation was appreciated fully.
Source: Heart Rhythm - Category: Cardiology Authors: Source Type: research
Publication date: Available online 6 February 2020Source: Stem Cell ResearchAuthor(s): Hong-Mei Zhou, Xiao-Qian Zhou, Ji-Zhen Lu, Wen-Wen Jia, Jiu-Hong KangAbstractLong QT syndrome type 8 is an uncommon inherited condition .An induced pluripotent stem cell (iPSC) line was generated from Peripheral blood mononuclear cells (PBMCs) of a 10-year-old patient with heterozygous mutation of p.R858H(c.2573G>A )in the CACNA1C gene. This iPSC model offers a very valuable resource to study the disease pathophysiology and to develop therapeutics for treatment of Long QT syndrome type 8 patients.
Source: Stem Cell Research - Category: Stem Cells Source Type: research
NIH-funded ClinGen panel also validates three genes believed to be associated with Long QT syndrome.
Source: National Institutes of Health (NIH) News Releases - Category: American Health Source Type: news
PMID: 31983240 [PubMed - as supplied by publisher]
Source: Circulation - Category: Cardiology Authors: Tags: Circulation Source Type: research
Acquired long QT syndrome is a well-described pathology in the pediatric population. Previous publications demonstrated that patients undergoing hematopoietic stem cell transplantation (HSCT) can develop cardiac complications, and several of these patients develop drug-induced long QT syndrome in the post-transplant period. Previous publications suggest that HSCT patients present significant QT prolongation in the early post-transplantation period.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 184 Source Type: research
lini C, Shimamoto K, Tadros R, Cadrin-Tourigny J, Duff HJ, Simpson CS, Roston TM, Wijeyeratne YD, El Hajjaji I, Yousif MD, Gula LJ, Leong-Sit P, Chavali N, Landstrom AP, Marcus GM, Dittmann S, Wilde AAM, Behr ER, Tfelt-Hansen J, Scheinman MM, Perez MV, Kaski JP, Gow RM, Drago F, Aziz PF, Abrams DJ, Gollob MH, Skinner JR, Shimizu W, Kaufman ES, Roden DM, Zareba W, Schwartz PJ, Schulze-Bahr E, Etheridge SP, Priori SG, Ackerman MJ Abstract Background: Insight into type 5 long QT syndrome (LQT5) has been limited to case reports and small family series. Improved understanding of the clinical phenotype and genetic featu...
Source: Circulation - Category: Cardiology Authors: Tags: Circulation Source Type: research
We examined frequency, clinical characteristics and AF‐related management and outcomes amongst this patient population.MethodsWe retrospectively studied consecutive probands with inherited cardiomyopathy (n=962) and inherited arrhythmia syndromes (n=195) evaluated between 2002 ‐2018.ResultsAF was observed in 5 ‐31% of patients, with the highest frequency in HCM. Age of AF onset was 45.8 ± 21.9 years in the inherited arrhythmia syndromes compared to 53.3 ± 15.3 years in the inherited cardiomyopathies, with 4 CPVT patients developing AF at median age of 20 years. Overall, 11% of patients with AF had a t r...
Source: Journal of Cardiovascular Electrophysiology - Category: Cardiology Authors: Tags: ORIGINAL ARTICLE Source Type: research
In this study, dynamical mechanisms of EAD formation in human ventricular myocytes (HVMs) were investigated using the mathematical model developed by ten Tusscher and Panfilov (Am J Physiol Heart Circ Physiol 291, 2006). We explored how the rapid (IKr) and slow (IKs) components of delayed-rectifier K+ channel currents, L-type Ca2+ channel current (ICaL), Na+/Ca2+ exchanger current (INCX), and intracellular Ca2+ handling via the sarcoplasmic reticulum (SR) contribute to initiation, termination and modulation of phase-2 EADs during pacing in relation to bifurcation phenomena in non-paced model cells. Parameter-dependent dyna...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Diagnosing long-QT syndrome (LQTS) remains challenging due to a considerable overlap in QT-interval between LQTS and healthy subjects. Characterizing T-wave morphology might improve LQTS diagnosis.
Source: Heart Rhythm - Category: Cardiology Authors: Source Type: research
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