LQT1 is a subtype of LQTS caused by mutations in KCNQ1, affecting the slow delayed-rectifier potassium current (<i>I</i><sub>Ks</sub>), which is essential for cardiac repolarization.
Loss-of-function (LOF) mutations in KCNQ1 are the most common cause of congenital long QT syndrome (LQTS), type 1 LQTS, an inherited genetic predisposition to cardiac arrhythmia and sudden cardiac death.
To establish a KCNQ1 mutant-specific induced pluripotent stem cell (iPSC) model of a Chinese inherited long QT syndrome (LQTS) patient and to explore the pathogenesis of KCNQ1 mutations.
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).
Several mutations linked to the LQTS have been identified, the most common of which have been found in the potassium channel KCNQ1 (LQT1) and hERG (LQT2) genes and in the sodium channel SCN5A (LQT3) gene.
We report three novel variants (KCNQ1 p.46, KCNH2 p.D803Y, SCN5A p.G1391R) which have never been reported for this AA location in LQTS; the phenotype-genotype correlation suggests their pathogenicity.
At least 16 genes have been implicated in LQTS; the yield of genetic analysis of 3 genes (KCNQ1, KCNH2, and SCN5A) is about 70%, with KCNQ1 mutations accounting for ∼50% of positive cases.
This study describes one physiological form of KCNQ1, depolarized voltage sensors with a closed pore in the absence of PIP<sub>2</sub>, and reveals a regulatory interaction between CaM and KCNQ1 that may explain CaM-mediated LQTS.
Four patients had LQTS type 1, 6 had LQTS type 2, and 1 had a disease-associated mutation in KCNQ1 and a variant of unknown significance in KCNH2 gene.
We assessed the clinical course and the fulfillment of current treatment strategies in molecularly defined pediatric LQTS type 1 and (LQT1) and type 2 (LQT2) patients.
The most frequent type of congenital long QT syndrome is LQT1, which is caused by mutations in the gene (KCNQ1) that encodes the alpha subunit of the slow component of delayed rectifier K(+) current (IKs) channel.
This study demonstrates that SNPs in NOS1AP and KCNQ1 are associated with an increased risk of cardiac events in LQTS patients, with the hazard ratio suggesting they have significant potential in clinical risk stratification.
In this review, we summarize the characteristics of LQTS (mainly LQT1-3) and briefly describe the most recent advances in LQTS clinical diagnostics as well as genetics.
A Chinese family diagnosed with LQTS were screened for KCNQ1, HERG and SCN5A, using polymerase chain reaction (PCR), direct sequencing, and clong sequencing.
Genotyping of 4 main LQTS-susceptibility genes (KCNQ1, KCNH2, KCNE1, and KCNE2) was performed here for the first time in SUNDS victims from the Chinese Han population to address the pathogenic cause of some SUNDS using polymerase chain reaction and direct DNA sequencing.120 sporadic SUNDS cases were enrolled.
The genetic spectrum of LQTS in 44 South African cLQTS patients (23 known to carry the South African founder mutation p.A341V in KCNQ1) was established by screening for mutations in the coding regions of KCNQ1, KCNH2, KCNE1, KCNE2 and SCN5A, the most frequently implicated cLQTS-causing genes (five-gene screening).
The medical records of 196 consecutive patients with symptomatic LQTS (age, 32 ± 19 years; female, n=133; LQT1, n=86; LQT2, n=95; LQT3, n=15) who were genotyped between 1979 and 2006 at 2 major Japanese institutions were retrospectively analyzed.
Efficiency of high resolution melting (HRM) analysis was evaluated for the most prevalent LQTS-causing genes (KCNQ1, KCNH2) using control DNAs and DNAs carrying previously identified gene variants.
Multivariate analysis was carried out to identify age-related gender- and genotype-specific risk factors for cardiac events (comprising syncope, aborted cardiac arrest [ACA] or sudden cardiac death [SCD]) from birth through age 40 years among 971 LQT1 (n = 549) and LQT2 (n = 422) patients from the International LQTS Registry.