The sodium channel gene SCN5A and potassium channel genes KCNQ1 and KCNH2 have been widely reported to be genetic risk factors for arrhythmia including Brugada syndrome and long QT syndrome (LQTS).
In this study, we analyzed the genetic variants of KCNQ1, KCNH2, and SCN5A in patients from seven cohorts (total N = 11945, including patients clinically suspected to have inherited arrhythmia [n = 122], other cardiovascular diseases [n = 1045], epilepsy [n = 4797], or other diseases [n = 5841], and healthy controls [n = 140]) who had undergone genetic testing.
Some normal-hearing carriers of heterozygous missense variants of KCNE1 and KCNQ1 have prolonged QT intervals, a dominantly inherited phenotype designated Romano-Ward syndrome (RWS), which is also associated with arrhythmias and elevated risk of sudden death.
We validated and optimized the NGS platform with a subset of 46 patients by comparison with Sanger sequencing of coding exons of major arrhythmia risk-genes (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, RYR2).
Long QT Syndrome type 1 (LQT1), an inherited cardiac ion channelopathy associated with arrhythmias and risk of sudden death, is caused by mutations in KCNQ1 encoding the α-subunit of Kv7.1, that affects the slow component of delayed rectifier K<sup>+</sup> current (I<sub>Ks</sub>) channel.
Mutations that induce loss of function (LOF) or dysfunction of the human KCNQ1 channel are responsible for susceptibility to a life-threatening heart rhythm disorder, the congenital long QT syndrome (LQTS).
In MI mice, sEHI t-AUCB can repress miR-133, consequently stimulating KCNQ1 and KCNH2 mRNA and protein expression, suggesting a possible mechanism for its potential therapeutic application in ischemic arrhythmias.
Our data suggest that use of NPSs, particularly synthetic cathinones, is associated with elevated risk of serious cardiac arrhythmia and sudden death for subjects carrying KCNQ1G643S.
A specialized inherited arrhythmia clinic is the preferred resource for the complex risk stratification and individualized management of individuals with LQT.
This study further substantiates a causal link between the V307LKCNQ1 mutation and pro-arrhythmia in human ventricles, and establishes partial inhibition of I<sub>Ks</sub> as a potential anti-arrhythmic strategy in SQT2.
We demonstrate dual LQT1 and HCM phenotypes in this multiple LQT1- and HCM-related gene mutation carrier family for the first time and suggest that LQT-related gene mutations associate with QT interval prolongation and/or arrhythmia in HCM patients.
The asymptomatic MCs differed significantly from the symptomatic MCs and from NMCs in less vagal control of heart rate and more reactive sympathetic modulation of the QT interval, particularly during daytime when arrhythmia risk for patients with LQT1 is greatest.
We have investigated mechanisms by which the S1 domain S140GKCNQ1 mutation influences atrial arrhythmia risk and, additionally, whether it can affect ventricular electrophysiology.
Seven infants with potentially lethal arrhythmias at age < 1 year (5 males, age of onset 44.1 ± 72.1 days) were genetically analyzed for KCNQ1, KCNH2, KCNE1-5, KCNJ2, SCN5A, GJA5, and CALM1 by using denaturing high-performance liquid chromatography and direct sequencing.
A total of 2 novel non-synonymous mutations and 3 previously reported arrhythmia susceptibility polymorphisms were identified in KCNQ1, KCNH2, KCNE1, and KCNE2.
Heterozygous mutations in KCNQ1 cause type 1 long QT syndrome (LQT1), a disease characterized by prolonged heart rate-corrected QT interval (QTc) and life-threatening arrhythmias.
Arrhythmia formation in subclinical ("silent") long QT syndrome requires multiple insults: quantitative mechanistic study using the KCNQ1 mutation Q357R as example.
In conclusion, increased I(Ks) due to the KCNQ1S140G mutation increases atrial susceptibility to arrhythmia due to increased tissue vulnerability, shortened ERP and altered atrial conduction velocity, which, in combination, facilitate initiation and maintenance of re-entrant excitation waves.
Inherited Long QT Syndrome (LQTS), a cardiac arrhythmia that predisposes to the often lethal ventricular fibrillation, is commonly linked to mutations in KCNQ1.
To detect single nucleotide polymorphisms (SNP) in SCN5A, KCNQ1 and KCNE1 of post-MI patients, and to assess whether they are related to electrophysiological markers of cardiac arrhythmia (QT interval) and the clinical course.