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

Christina G. Loporcaro, David J. Tester, Joseph J. Maleszewski, Teresa Kruisselbrink, Michael J. Ackerman

Research output: Contribution to journalArticle

41 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)1083-1089
Number of pages7
JournalArchives of Pathology and Laboratory Medicine
Volume138
Issue number8
DOIs
StatePublished - Aug 2014

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medical Laboratory Technology

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