Identifying the Pathogenic Variants in Heart Genes in Vietnamese Sudden Unexplained Death Victims by Next-Generation Sequencing

• Published in: Diagnostics (Basel) Vol. 14; no. 17; p. 1876
• Main Authors: Nguyen Tat, Tho, Lien, Nguyen Thi Kim, Luu Sy, Hung, Ta Van, To, Dang Viet, Duc, Nguyen Thi, Hoa, Tung, Nguyen Van, Thanh, Le Tat, Xuan, Nguyen Thi, Hoang, Nguyen Huy
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27.08.2024
• Subjects: Autopsies; Cardiac arrhythmia; cardiac channelopathies; cardiomyopathies; Cardiomyopathy; Cardiovascular disease; Forensic medicine; Forensic sciences; Genes; Genetic testing; Genomes; Genomics; Heart; Ischemia; Kinases; Long QT syndrome; molecular autopsy; Mutation; next-generation sequencing (NGS); sudden unexplained death (SUD); Vietnamese victims; United States > US; sudden unexplained death (SUD); Vietnamese victims; cardiomyopathies; next-generation sequencing (NGS); cardiac channelopathies; molecular autopsy
• ISSN: 2075-4418; 2075-4418
• DOI: 10.3390/diagnostics14171876

In forensics, one-third of sudden deaths remain unexplained after a forensic autopsy. A majority of these sudden unexplained deaths (SUDs) are considered to be caused by inherited cardiovascular diseases. In this study, we investigated 40 young SUD cases (<40 years), with non-diagnostic structural cardiac abnormalities, using Targeted NGS (next-generation sequencing) for 167 genes previously associated with inherited cardiomyopathies and channelopathies. Fifteen cases identified 17 variants on related genes including the following: , , , , , , , , , , , , , , , and . Of these, eight variants were novel, and nine variants were reported in the ClinVar database. Five were determined to be pathogenic and four were not evaluated. The novel and unevaluated variants were predicted by using in silico tools, which revealed that four novel variants (c.5187_5188dup, p.Arg1730llefsTer4 in the gene; c.1454A>T, p.Lys485Met in the gene; c.2535+1G>A in the gene; and c.10498G>T, p.Asp3500Tyr in the gene) were pathogenic and three variants (c.292C>G, p.Arg98Gly in the gene; c.683C>A, p.Pro228His in the gene; and c.2275G>A, p.Glu759Lys in the gene) still need to be further verified experimentally. The results of our study contributed to the general understanding of the causes of SUDs. They provided a scientific basis for screening the risk of sudden death in family members of victims. They also suggested that the Targeted NGS method may be used to identify the pathogenic variants in SUD victims.