Sudden death and Next Generation Sequencing: a review

Abstract

Introduction: Sudden death is a fatal and unpredictable event. After autopsy and complementary studies, in the absence of other findings that explain the cause of death, it is classified as sudden unexplained death. It is advisable in these cases to perform genetic analysis, especially with next generation sequencing methodologies, which can explain a significant percentage of these cases. Objective: to analyze the most relevant publications regarding NGS applied to molecular autopsy to determine sudden unexplained deaths related to cardiomyopathies and channelopathies. Methodology: A search was performed in PubMed of the National Institute of Health using keywords in English and Spanish: NGS, sudden death, molecular autopsy, and combinations. In addition, OMIN and ClinVar were searched for the different cardiac conditions related to sudden death. Inclusion criteria: complete articles in Spanish and English, open access, not older than 10 years, published in any geographic area and dealing with the subject. Results: For next-generation sequencing and sudden death, more than 22,000 and 65,000 publications were found, respectively. In contrast, combined were 74 papers, where the application of sequencing platforms in the investigation of sudden death cases started in 2014. In a short time, they demonstrated their versatility for the analysis of many genes simultaneously, quickly and at low cost. According to the inclusion criteria and objective of the work, 67 articles were reviewed. Conclusions: The pathologies associated with sudden death are multiple, complex and can generate variable phenotypes that make their genetic analysis difficult. Next-generation sequencing platforms are extremely useful in cases of unexplained sudden death, and allow the identification of genetic variants in family members for the implementation of preventive measures.