1. Confirmation of cause and manner of death via a comprehensive cardiac autopsy including whole exome next-generation sequencing.
- Author
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Loporcaro CG, Tester DJ, Maleszewski JJ, Kruisselbrink T, and Ackerman MJ
- Subjects
- Adolescent, Amino Acid Substitution, Autopsy, Cardiac Myosins metabolism, Cardiomyopathy, Hypertrophic, Familial metabolism, Cardiomyopathy, Hypertrophic, Familial pathology, Cardiomyopathy, Hypertrophic, Familial physiopathology, DNA chemistry, DNA metabolism, Death, Sudden etiology, Exome, Female, High-Throughput Nucleotide Sequencing, Humans, Myocardium metabolism, Myosin Heavy Chains metabolism, Sequence Analysis, DNA, Cardiac Myosins genetics, Cardiomyopathy, Hypertrophic, Familial genetics, Cause of Death, Mutation, Myocardium pathology, Myosin Heavy Chains genetics
- Abstract
Annually, the sudden death of thousands of young people remains inadequately explained despite medicolegal investigation. Postmortem genetic testing for channelopathies/cardiomyopathies may illuminate a potential cardiac mechanism and establish a more accurate cause and manner of death and provide an actionable genetic marker to test surviving family members who may be at risk for a fatal arrhythmia. Whole exome sequencing allows for simultaneous genetic interrogation of an individual's entire estimated library of approximately 30000 genes. Following an inconclusive autopsy, whole exome sequencing and gene-specific surveillance of all known major cardiac channelopathy/cardiomyopathy genes (90 total) were performed on autopsy blood-derived genomic DNA from a previously healthy 16-year-old adolescent female found deceased in her bedroom. Whole exome sequencing analysis revealed a R249Q-MYH7 mutation associated previously with familial hypertrophic cardiomyopathy, sudden death, and impaired β-myosin heavy chain (MHC-β) actin-translocating and actin-activated ATPase (adenosine triphosphatase) activity. Whole exome sequencing may be an efficient and cost-effective approach to incorporate molecular studies into the conventional postmortem examination.
- Published
- 2014
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