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 Maleszewski, Teresa Kruisselbrink, Michael John Ackerman

Research output: Contribution to journalArticle

36 Citations (Scopus)

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 - 2014

Fingerprint

Exome
Cause of Death
Autopsy
Channelopathies
Sudden Death
Cardiomyopathies
Actins
Familial Hypertrophic Cardiomyopathy
Genes
Myosin Heavy Chains
Genetic Testing
Genetic Markers
Adenosine Triphosphatases
Cardiac Arrhythmias
Costs and Cost Analysis
Mutation
DNA

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medical Laboratory Technology

Cite this

Confirmation of cause and manner of death via a comprehensive cardiac autopsy including whole exome next-generation sequencing. / Loporcaro, Christina G.; Tester, David J.; Maleszewski, Joseph; Kruisselbrink, Teresa; Ackerman, Michael John.

In: Archives of Pathology and Laboratory Medicine, Vol. 138, No. 8, 2014, p. 1083-1089.

Research output: Contribution to journalArticle

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