Key result
Whole exome sequencing identified 7 possible pathological single nucleotide variants in cardiac disease-associated genes among 5 families with a history of sudden unexplained death.
Why the study?
The study was conducted to explore the causes of sudden unexpected death and to search for high-risk people using whole exome sequencing in affected families.
Observational (n=25)
Whole exome sequencing identified potentially pathogenic variants in cardiac genes among families with sudden unexplained death, highlighting the importance of genetic screening combined with ECG monitoring for prevention.
May inform family screening after sudden unexplained death; leaves open validation of variants in larger cohorts.
OBJECTIVES: To explore the causes of sudden unexpected death (SUD) and to search for high-risk people, whole exome sequencing (WES) was performed in families with SUDs. METHODS: Whole exome sequencing of 25 people from 14 SUD families were screened based on cardiac disease-associated gene variants, and their echocardiograms and electrocardiograms (ECG) were also examined. The protein function of mutated genes was predicted by SIFT, PolyPhen2 and Mutation Assessor. RESULTS: In the group of 25 people from 14 SUD families, 49 single nucleotide variants (SNVs) of cardiac disease-associated genes were found and verified by Sanger sequencing. 29 SNVs of 14 cardiac disorder-related genes were predicted as pathogens by software. Among them, 7 SNVs carried by two or more members were found in 5 families, including SCN5A (c.3577C > T), IRX4 (c.230A > G), LDB3 (c.2104 T > G), MYH6 (c.3G > A), MYH6 (c.3928 T > C), TTN (c.80987C > T) and TTN (c.8069C > T). 25 ECGs were collected. In summary, 4 people had J-point elevation, 2 people had long QT syndrome (LQTS), 4 people had prolonged QT interval, 3 people had T-wave changes, 3 people had sinus tachycardia, 4 people had sinus bradycardia, 4 people had left side of QRS electrical axis, and 3 people had P wave broadening. Echocardiographic results showed that 1 person had atrial septal defect, 1 person had tricuspid regurgitation, and 2 people had left ventricular diastolic dysfunction. CONCLUSIONS: Of the 14 heart disease-associated genes in 14 SUDs families, there are 7 possible pathological SNVS may be associated with SUDs. Our results indicate that people with ECG abnormalities, such as prolonged QT interval, ST segment changes, T-wave change and carrying the above 7 SNVs, should be the focus of prevention of sudden death.
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Wei et al. (2023) conducted an observational in Sudden unexplained death (SUD) family history (n=25). Whole exome sequencing was evaluated on Pathogenic single nucleotide variants (SNVs) of cardiac disease-associated genes. Whole exome sequencing identified 7 possible pathological single nucleotide variants in cardiac disease-associated genes among 5 families with a history of sudden unexplained death.
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