Identifying the Pathogenic Variants in Heart Genes in Vietnamese Sudden Unexplained Death Victims by Next-Generation Sequencing
Tho Nguyen Tat,
Nguyen Thi Kim Lien,
Hung Luu Sy,
To Ta Van,
Duc Dang Viet,
Hoa Nguyen Thi,
Nguyen Van Tung,
Le Tat Thanh,
Nguyen Thi Xuan,
Nguyen Huy Hoang
Affiliations
Tho Nguyen Tat
Department of Forensic Medicine, Hanoi Medical University, 1 Ton That Tung Str., Dongda, Hanoi 100000, Vietnam
Nguyen Thi Kim Lien
Institute of Genome Research, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet Str., Caugiay, Hanoi 100000, Vietnam
Hung Luu Sy
Department of Forensic Medicine, Hanoi Medical University, 1 Ton That Tung Str., Dongda, Hanoi 100000, Vietnam
To Ta Van
Department of Pathology, National Cancer Hospital, 43 Quan Su Str., Hoan Kiem, Hanoi 100000, Vietnam
Duc Dang Viet
Cardiovascular Intensive Care Unit, Heart Institute, 108 Military Central Hospital, 1B Tran Hung Dao Str., Hai Ba Trung, Hanoi 100000, Vietnam
Hoa Nguyen Thi
Faculty of Biotechnology, Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Str., Caugiay, Hanoi 100000, Vietnam
Nguyen Van Tung
Institute of Genome Research, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet Str., Caugiay, Hanoi 100000, Vietnam
Le Tat Thanh
Institute of Genome Research, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet Str., Caugiay, Hanoi 100000, Vietnam
Nguyen Thi Xuan
Institute of Genome Research, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet Str., Caugiay, Hanoi 100000, Vietnam
Nguyen Huy Hoang
Institute of Genome Research, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet Str., Caugiay, Hanoi 100000, Vietnam
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 (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.
