Development of a cardiac channel molecular autopsy in a South African cohort of sudden unexplained deaths in the young

Abstract

Sudden cardiac death is deemed a major global public health concern. In sub-Saharan Africa, including South Africa, there is a lack of reliable statistics on the incidence of SCD, even though a fourfold increase in noncommunicable diseases, largely due to cardiovascular diseases, has been reported. Considering that sudden cardiac deaths contribute to an estimated 50% of all cardiovascular deaths, it highlights South Africa’s need for research into better detection, treatment and prevention of sudden cardiac deaths. The aim of this study was to identify an inherited cardiac arrhythmogenic disorder, caused by variants in cardiomyopathy and arrhythmia-related genes, as a possible contributing factor to the cause of sudden cardiac deaths. Next generation sequencing identified a total of 178 different missense variants among the entire study population (n = 66);164 were known, documented variants whereas the remaining 14 were novel. A total of 127 variants were of like benign significance, 33 were variants of unknown significance, whereas the remaining six variants were of likely pathogenic significance. Post mortem genetic testing provided evidence of a genetic arrhythmic/cardiac conduction disorder as the probable pathogenic basis for 9% of sudden unexpected death / sudden unexplained infant death cases. Targeted next generation sequencing of 16 prevalent genes are recommended for routine testing in all unexplained sudden unexpected death / sudden unexpected infant death cases in South Africa.