A patient has a prolonged QTc interval of 510 ms. Which ion channel defect is most commonly associated with long QT syndrome Type 2 (LQT2)?
- A Loss-of-function mutation in KCNH2 (HERG) gene encoding the rapid delayed rectifier K+ channel (IKr), impairing phase 3 repolarisation ✓
- B Gain-of-function mutation in SCN5A encoding Nav1.5, increasing persistent late Na+ current (INaL) during the plateau phase
- C Loss-of-function mutation in KCNQ1 encoding the slow delayed rectifier K+ channel (IKs), prolonging repolarisation
- D Gain-of-function mutation in CACNA1C encoding L-type Ca2+ channels, prolonging the plateau
Explanation
Long QT syndrome Type 2 (LQT2) is caused by loss-of-function mutations in the KCNH2 gene, which encodes the alpha subunit of the hERG (human ether-a-go-go related gene) potassium channel responsible for the rapid delayed rectifier current (IKr). IKr is critical for phase 3 repolarisation; its loss prolongs the action potential duration and the QT interval. LQT2 is particularly sensitive to triggers such as auditory startle and emotional stress. LQT1 (option C) is caused by KCNQ1 (IKs) loss-of-function, triggered by exercise and swimming. LQT3 (option B) is SCN5A gain-of-function, causing late Na+ current. Option D is Timothy syndrome (LQT8).
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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