Confirmation of cause and manner of death via a comprehensive cardiac autopsy including whole exome next-generation sequencing

Arch Pathol Lab Med. 2014 Aug;138(8):1083-9. doi: 10.5858/arpa.2013-0479-SA. Epub 2013 Dec 3.


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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Amino Acid Substitution
  • Autopsy
  • Cardiac Myosins / genetics*
  • Cardiac Myosins / metabolism
  • Cardiomyopathy, Hypertrophic, Familial / genetics*
  • Cardiomyopathy, Hypertrophic, Familial / metabolism
  • Cardiomyopathy, Hypertrophic, Familial / pathology
  • Cardiomyopathy, Hypertrophic, Familial / physiopathology
  • Cause of Death*
  • DNA / chemistry
  • DNA / metabolism
  • Death, Sudden / etiology
  • Exome
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Mutation*
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Myosin Heavy Chains / genetics*
  • Myosin Heavy Chains / metabolism
  • Sequence Analysis, DNA


  • MYH7 protein, human
  • DNA
  • Cardiac Myosins
  • Myosin Heavy Chains