Inherited syndromes arising from rare genetic variants that cause cardiac arrhythmia (abnormal heart rhythm) are the most common cause of unexplained sudden death in people 15 to 30 years old. Yet it is difficult to distinguish benign (harmless) variants from those that are pathogenic.
Brett Kroncke, PhD, and colleagues in the Vanderbilt Center for Arrhythmia Research and the Victor Chang Cardiac Research Institute in Darlinghurst, Australia, used a massively parallel trafficking assay to characterize all variants in the “hotspot” of a potassium channel gene, KCNH2, that is associated with long QT syndrome.
While more than half of the variants were found to be functionally normal, the assay proved to be more accurate than bioinformatic prediction tools in discriminating between functional and abnormal variants, the researchers reported last month in The American Journal of Human Genetics.
By providing prospective information, the assay potentially may improve the ability to identify and preemptively treat individuals at risk for sudden cardiac death, the researchers concluded.
The study was supported in part by National Institutes of Health grant HL135442, the Leducq Foundation for Cardiovascular Research, the American Heart Association, and the New South Wales government.
