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.
KCNQ1 mutations associated with Jervell and Lange-Nielsen syndrome and autosomal recessive Romano-Ward syndrome in India-expanding the spectrum of long QT syndrome type 1.
KCNQ1 mutations associated with Jervell and Lange-Nielsen syndrome and autosomal recessive Romano-Ward syndrome in India-expanding the spectrum of long QT syndrome type 1.
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.
Recessive cardiac phenotypes in induced pluripotent stem cell models of Jervell and Lange-Nielsen syndrome: disease mechanisms and pharmacological rescue.