Next-generation sequencing of postmortem molecular markers to support for medicolegal autopsy

Abstract

In most cases, sudden unexplained death (SUD) is caused by hereditary cardiac arrhythmias that standard forensic autopsy procedures cannot prove. For this reason, forensics analysis must apply other methodologies to uncover related factors. For example, postmortem molecular analysis (molecular autopsy) based on next-generation sequencing represents a promising and effective tool for diagnosing SUD. This analysis allows scientists to detect well-known, new, and rare pathogenic exonic variants or those with unknown significance that could be related to the cause of sudden death. Using exome sequencing, we identified rare exon variants in MYBPC3, KCND3, TTN, and ANK3 in a fifteen-year-old male SUD case with negative toxicology analysis and autopsy showing microscopic abnormality of heart fiber disarray. Our findings suggested that this case might be associated with cardiac channelopathy long QT syndrome, type 2, as a potential causative factor.

Keywords

• SUD
• Cardiac Channelopathies
• LQTs
• NGS