Key result
Post-mortem genetic testing identified pathogenic or likely pathogenic variants linked to inherited cardiac arrhythmogenic disorders in approximately 4% (2 of 51) of young South African sudden unexpected death cases.
Why the study?
Sudden cardiac death accounts for an estimated 50% of cardiovascular deaths in South Africa, creating a need for research into inherited arrhythmogenic disorders to improve detection, treatment, and prevention.
Does post-mortem next-generation sequencing identify pathogenic genetic variants in young South African cases of sudden unexpected death?
Observational (n=51)
No
Does post-mortem next-generation sequencing identify pathogenic genetic variants in young South African cases of sudden unexpected death?
Post-mortem genetic testing using next-generation sequencing identified a probable pathogenic genetic basis in approximately 4% of young sudden unexpected death cases in a South African cohort.
Sudden cardiac death (SCD) is a major public health concern. In sub-Saharan Africa (SSA), including South Africa, there is a lack of reliable statistics on the incidence of SCD, even though there has been a fourfold increase in noncommunicable diseases (NCD), particularly cardiovascular diseases (CVD). Sudden cardiac death contributes to an estimated 50% of all cardiovascular deaths, which highlights South Africa's need for research into better detection, treatment and prevention. This study aimed to identify an inherited cardiac arrhythmogenic disorder, linked to variants in cardiomyopathy- and arrhythmia-related genes, as a potential contributing factor to sudden cardiac deaths. DNA was extracted from blood samples collected at autopsy of 51 sudden unexpected death (SUD) cases, and subjected to next-generation sequencing (NGS) of 49 genes linked to inherited cardiac arrhythmogenic disorders. Variants were annotated and interpretated for clinical significance using the Galaxy bioinformatic platform. In total, 175 different missense variants were identified in the study population (n = 51). Of these, 92.5% (162/175) were known, documented variants, and the remaining 7.4% (13/175) were considered novel. Of the known variants, 78.4% (127/162) were of benign/likely benign significance, 20.4% (33/162) were variants of unknown significance (VUS), and 1.2% (2/162) was pathogenic. The 13 novel variants were analysed using online prediction software, with 92.3% (12/13) predicted to be likely benign and 7.7% (1/13) grouped into the VUS category. Post-mortem genetic testing provided evidence of a genetic arrhythmic/cardiac conduction disorder as the probable pathogenic basis for approximately 4% (2/51) of sudden unexpected death (SUD) cases.
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Deventer et al. (2025) conducted an observational in Sudden unexpected death (SUD) (n=51). Post-mortem genetic testing (Next-generation sequencing) was evaluated on Identification of pathogenic or likely pathogenic variants linked to inherited cardiac arrhythmogenic disorders. Post-mortem genetic testing identified pathogenic or likely pathogenic variants linked to inherited cardiac arrhythmogenic disorders in approximately 4% (2 of 51) of young South African sudden unexpected death cases.
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