In patients with subclinical mutations in the KCNQ1 or
KCNH2 genes, certain antiarrhythmics may be the trigger for LQTS.
For example, cardiomyocytes of a patient having the R176W mutation in
KCNH2 demonstrate a significant increase in action and field potentials but do not show any signs of early afterdepolarization, which agrees with the absence of arrhythmic events in this patient [29].
demonstrated a similar mutation rate in the
KCNH2, KCNQ1, and SCN5A cardiac conduction genes in acquired LQTS compared to congenital LQTS [6].
Nicodemus et al., "A primate-specific, brain isoform of
KCNH2 affects cortical physiology, cognition, neuronal repolarization and risk of schizophrenia," Nature Medicine, vol.
Mutations in potassium (
KCNH2, KCNQ1, KCNJ2) and calcium channel subunit genes have been identified to cause short QT syndrome (SQTS) (34), which is a rare, sporadic, or autosomal dominant disorder characterized by markedly accelerated cardiac repolarization and is manifested by a dramatically shortened QT interval, atrial and ventricular arrhythmias, and sudden cardiac death.
cerevisiae]), PCSK9 (proprotein convertase subtilisin/kexin type 9), and
KCNH2 (potassium voltage-gated channel, subfamily H [eagrelated], member 2)] for which >20% of HGMD variants had a median inadequate ([less than or equal to] 20X) depth of coverage.
Of the 16 LQTS SIDS cases, 8 featured a mutation in SCNSA, 6 in
KCNH2, and 2 in KCNQ1.
A561P
KCNH2 mutation caused a trafficking defect of the HERG channel.
The nonsynonymous coding IKr-channel variant KCNH2-K897T is associated with atrial fibrillation: results from a systematic candidate gene-based analysis of
KCNH2 (HERG).
About 40% of LQTS patients show aberrations in LQT2-associated gene locus for
KCNH2 encoding the [alpha]-subunit of the [I.sub.Kr] channel, linked to chromosome 7 [29].
Among these patients, 20-40% may have mutations in
KCNH2 encoding the HERG [alpha]-subunit of the HERG/MiRP1 channel conducting the [I.sub.Kr], current, and 30-50% may have mutations in KCNQ1 encoding the KvLQT1 [alpha]-subunit of the KvLQT1/minx channel conducting the [I.sub.Ks] current (7).