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CPVT: Difference between revisions
→Genetic diagnosis
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==Genetic diagnosis== | ==Genetic diagnosis== | ||
[[Image:CPVT. | [[Image:CPVT.svg|thumb|200px|left|Intraluminal calcium as a primary regulator of endoplasmic reticulum function 2005<cite>CellCalcium</cite>]] | ||
CPVT is caused by mutations in genes involved in the calcium homeostasis of cardiac cells. Four disease-causing genes have been identified: the ryanodine<cite>ryanodine</cite> receptor 2 gene (RyR2) (60%), the cardiac calsequestrin 2 gene (CASQ2) (1-2%), the calmodulin gene (CALM1) (<1%) and the TRDM gene (<1%). Mutant RyR2 channels have a gain-of-function effect, resulting in excessive calcium release during sympathetic activation. Mutant CASQ2 causes loss of buffering capacity for calcium of the sarcoplasmatic reticulum. The mutations cause excessive calcium in the myocyte cytosol generating depolarizing membrane currents, which in turn lead to delayed afterdepolarizations and cardiac arrhythmias. | CPVT is caused by mutations in genes involved in the calcium homeostasis of cardiac cells. Four disease-causing genes have been identified: the ryanodine<cite>ryanodine</cite> receptor 2 gene (RyR2) (60%), the cardiac calsequestrin 2 gene (CASQ2) (1-2%), the calmodulin gene (CALM1) (<1%) and the TRDM gene (<1%). Mutant RyR2 channels have a gain-of-function effect, resulting in excessive calcium release during sympathetic activation. Mutant CASQ2 causes loss of buffering capacity for calcium of the sarcoplasmatic reticulum. The mutations cause excessive calcium in the myocyte cytosol generating depolarizing membrane currents, which in turn lead to delayed afterdepolarizations and cardiac arrhythmias. | ||