Article Citation:

Christina G. Loporcaro, David J. Tester, Joseph J. Maleszewski, Teresa Kruisselbrink, and Michael J. Ackerman (2013) Confirmation of Cause and Manner of Death Via a Comprehensive Cardiac Autopsy Including Whole Exome Next-Generation Sequencing. Archives of Pathology & Laboratory Medicine In-Press.

Early Online Release

Confirmation of Cause and Manner of Death Via a Comprehensive Cardiac Autopsy Including Whole Exome Next-Generation Sequencing

Christina G. Loporcaro , BS; David J. Tester , BS; Joseph J. Maleszewski , MD; Teresa Kruisselbrink , MS; Michael J. Ackerman ,MD, PhD

From the Mayo Medical School, Rochester, Minnesota (Ms Loporcaro); the Departments of Internal Medicine/Division of Cardiovascular Diseases (Mr Tester and Dr Ackerman), Laboratory Medicine & Pathology, Division of Anatomic Pathology (Dr Maleszewski), Laboratory Medicine & Pathology, Division of Laboratory Genetics (Ms Kruisselbrink), Molecular Pharmacology & Experimental Therapeutics (Dr Ackerman), and Pediatric and Adolescent Medicine/Division of Pediatric Cardiology (Dr Ackerman), and the Windland Smith Rice Sudden Death Genomics Laboratory (Mr Tester and Dr Ackerman), Mayo Clinic, Rochester, Minnesota.

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 30 000 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.