After ATO treatment, the Kcnq1ot1 and Kcnq1 expression levels were down regulated. lncRNA Kcnq1ot1 knockdown prolonged the action potential duration (APD) in vitro and exerted LQTS in vivo.
Type, frequency, and location of mutations across KCNQ1 (LQT1), KCNH2 (LQT2), and SCN5A (LQT3) were compared between 388 unrelated "definite" (clinical diagnostic score >or=4 and/or QTc >or=480 ms) cases of LQTS and >1300 healthy controls for each gene.
The SCN5A mutations have been associated with a variety of arrhythmic disorders, including type 3 long QT syndrome (LQT3), Brugada syndrome and inherited cardiac conduction defects.
Among VCG parameters, QTpeak and TwEVs significantly differentiated patients with ecLQTS from controls (P ≤ .01 for each) as well as differentiated KCNQ1-encoded type 1 LQTS (ecLQT1), KCNH2-encoded type 2 LQTS (ecLQT2), and SCN5A-encoded type 3 LQTS (ecLQT3) from controls (P < .01). ecLQT3 was differentiated from controls and ecLQT1 and ecLQT2 by the fourth TwEV (P < .01 for each).
To test the hypothesis that autonomic maneuvers can unmask long QT syndrome in genetically abnormal subjects with a normal phenotype (QTc < or =450 ms), we exposed 13 controls (33 +/- 9 years; 5 men), 5 patients with LQT1 (32 +/- 12 years; 3 men), and 5 patients with LQT2 (30 +/- 11 years; 5 men) to phenylephrine bolus, exercise, and epinephrine infusion.
As proof-of-concept we extracted the wild-type and mutant of exon 12 and exon 17 of SCN5A genetic DNA from patients with long QT syndrome or Brugada syndrome by touchdown PCR and performed a successful point mutation discrimination in the AMDM platform.
Rate-dependent facilitation of K(+) conductance, a key property of I(Ks) that enables action potential shortening at higher heart rates, was defective for both KCNE1 C-terminal mutations, and may contribute to the clinical phenotype of arrhythmias triggered by heart rate elevations during exercise in LQTS mutations.
Mutations in SCN5A lead to a large spectrum of phenotypes, including long-QT syndrome, Brugada syndrome, and isolated progressive cardiac conduction defect (Lenègre disease).
Recently, the genes for the LQTS inked to chromosomes 3 (LQT3), 7 (LQT2), and 11 (LQT1) were identified as SCN5A, the cardiac sodium channel gene and as HERG and KvLQT1 potassium channel genes.
The study cohort consisted of 67 KCNQ1 mutation carriers and 13 family members who were suspected as having LQTS due to sudden cardiac death or syncope from 36 unrelated families.
Mutations in HERG and KCNQ1 potassium channels have been associated with Long QT syndrome and atrial fibrillation, and more recently with sudden infant death syndrome and sudden unexplained death.
The coding regions of genes KCNQ1, KCNH2 and SCN5A in patients with LQTS and their family members were sequenced and analyzed using Geneious ProTM software.