We obtained high-quality DNA from 70 cases, which were then sequenced for a custom panel of 35 genes, 12 for inherited long- and short-QT syndrome genes (LQT1-LQT12 and SQT1-3), and 23 additional candidate genes derived from genome-wide association studies.
Atrial fibrillation (AF) and sinus bradycardia have been reported in patients with short QT syndrome variant 2 (SQT2), which is underlain by gain-of-function mutations in <i>KCNQ1</i> encoding the α subunit of channels carrying slow delayed rectifier potassium current, <i>I</i><sub>Ks</sub>.
Loss-of-function mutations in the gene KCNQ1 encoding the Kv7.1 K(+) channel cause long QT syndrome type 1 (LQT1), whereas gain-of-function mutations are associated with short QT syndrome as well as familial atrial fibrillation (FAF).
This simulation study identifies mechanisms by which cellular electrophysiological changes in the SQT2 (slow delayed rectifier, IKs, -linked) SQTS variant increases arrhythmia risk.
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.
Three different gain-of-function mutations in genes encoding for cardiac potassium channels (KCNH2, KCNQ1, and KCNJ2) have been identified up to now to cause short QT syndrome.