As an exemplar, the c.1750G > A; p.Gly584Ser variant within the coding sequence of the KCNH2 gene implicated in Long QT Syndrome (LQTS), which occurred once in 500 whole genome sequences from this population, was investigated.
A missense mutation (G604S) in the S5/pore region of HERG causes long QT syndrome in a Chinese family with a high incidence of sudden unexpected death.
Three heterozygous LQT-2 patients (KCNH2-p.Arg752Pro missense mutation) and two unaffected family members additionally were studied during their menstrual cycles.
These data suggest that R863Xfailed to form functional HERG channels, contributing to a prolongation of the QT interval and long QT syndrome with a dominant phenotype.
In this study, we investigated the pathogenic mechanism of the hERG splice site mutation 2398+1G>C and the genotype-phenotype relationship of mutation carriers in three unrelated kindreds with long QT syndrome.
Patient-specific hiPSCs were generated from a symptomatic SQTS patient carrying the N588K mutation in the KCNH2 gene, differentiated into cardiomyocytes, and compared with healthy and isogenic (established by CRISPR/Cas9-based mutation correction) control hiPSC-derived cardiomyocytes (hiPSC-CMs).
Hence, unlike the known mutations in the two other SQTS forms (N588K in HERG and V307L in KvLQT1), simulations using the D172N and WT/D172N mutations fully accounted for the ECG phenotype of tall and asymmetrically shaped T waves.
Here, for the first time, electrophysiological effects were studied of a gain-of-function hERG mutation (N588K; responsible for the 'SQT1' variant of the short QT syndrome) on current (I(hERG1a/1b)) carried by co-expressed hERG1a/1b channels.
To evaluate the electrophysiological consequences of the short-QT syndrome at the level of the cardiac AP, the Markov model of wild-type (WT) KCNH2 channel was modified to obtain a model of the KCNH2 channel with the N588K mutation associated with the short-QT syndrome.
In this study, we used the oocyte expression system and voltage clamp techniques to determine the functional consequences of eight long QT syndrome-associated mutations located in the amino-terminal region of HERG (F29L, N33T, G53R, R56Q, C66G, H70R, A78P, and L86R).
A genetic variant (rs3800779; M30) in the KCNH2 gene has been associated with schizophrenia, a lower intelligence quotient (IQ) and processing speed scores, altered brain functions and increased KCNH2-3.1. mRNA levels in the hippocampus.
We genotyped four single nucleotide polymorphisms (SNPs) in 7q36.1 region (two SNPs, rs1805123 and rs3800779, located on HERG1, and two SNPs, rs885684 and rs956642, at the 3'-downstream intergenic region) and then performed single SNP and haplotype association analyses in 84 patients with schizophrenia and 74 healthy controls after the exclusion of individuals having prolonged or shortened QT interval on electrocardiogram.
Domestic pigs received AdKCNH2-G628S by epicardial atrial gene painting and atrial pacemaker implantation for continuous-burst pacing to induce atrial fibrillation.