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 .
demonstrated a similar mutation rate in the KCNH2
, KCNQ1, and SCN5A cardiac conduction genes in acquired LQTS compared to congenital LQTS .
Nicodemus et al., "A primate-specific, brain isoform of KCNH2
affects cortical physiology, cognition, neuronal repolarization and risk of schizophrenia," Nature Medicine, vol.
The result showed that 11 overlapping proteins (ACACA, ampC, APP, BCL2, CDK2, FASN, gyrB, katA, KCNH2
, MAPK3, and NR3C1) were related to many different biological functions including oxidoreductase activity, MAP kinase activity, and NF-kappa-B binding (Figure 11(a)).
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.
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
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 .
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).