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>.
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.
This simulation study identifies mechanisms by which cellular electrophysiological changes in the SQT2 (slow delayed rectifier, IKs, -linked) SQTS variant increases arrhythmia risk.
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.
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).