| Abstrakt: |
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: AKAP9, CSRP3, GSN, HTRA1, KCNA5, LAMA4, MYBPC3, MYH6, MYLK, RYR2, SCN5A, SCN10A, SLC4A3, TNNI3, TNNI3K, and TNNT2. 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 AKAP9 gene; c.1454A>T, p.Lys485Met in the MYH6 gene; c.2535+1G>A in the SLC4A3 gene; and c.10498G>T, p.Asp3500Tyr in the RYR2 gene) were pathogenic and three variants (c.292C>G, p.Arg98Gly in the TNNI3 gene; c.683C>A, p.Pro228His in the KCN5A gene; and c.2275G>A, p.Glu759Lys in the MYBPC3 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. [ABSTRACT FROM AUTHOR] |
