An overview of the genetic variations associated with the pathophysiology and mechanisms of sudden cardiac death
Keywords:
Sudden Cardiac Death, KCNQ1, SCN5A, Long QT syndrome, Cardiac geneticAbstract
Sudden cardiac death (SCD) is one of the commonest causes of death among young adults. Cardiac arrhythmias secondary to channelopathies are one of the main causes of SCD. Channelopathies is a condition where there are abnormalities of one or more ion channels involved in the cardiac action potential. These ion channels are strictly regulated and encoded by a specific gene for each channel. As for current knowledge, KCNQ1, SCN5A, CACN1AC, CALM1, and RYR2 are the most studied genetic mutation in inherited sudden cardiac death patient. There are five most common chromosomes involved in this condition namely chromosome 1q42 to q43, 3p21, 7,11, and 12 which encodes RYR2, SCN5A, KCNH, KCNQ1 and CACN1AC respectively. Two most common types of genetic mutation involved are loss-of -function mutation and missense mutations. Any disturbance in channel morphology or function due to genetic mutation will lead to channelopathies for example SCN5A gene gain function mutation in Long QT syndrome. This condition is an inherited disorder and mainly inherited by autosomal dominant. Therefore, genetic linkage study by cascade family screening is important for the early detection of this condition and to reduce the risk of sudden cardiac death among young patients.
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