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Title: Exome sequencing-based molecular autopsy of formalin-fixed paraffin-embedded tissue after sudden death.
Austin Authors: Bagnall, Richard D;Ingles, Jodie;Yeates, Laura;Berkovic, Samuel F ;Semsarian, Christopher
Affiliation: Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Sydney, Australia
Sydney Medical School, University of Sydney, Sydney, Australia
Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia
Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Issue Date: Oct-2017 2017-03-23
Publication information: Genetics in medicine : official journal of the American College of Medical Genetics 2017; 19(10): 1127-1133
Abstract: Sudden death in the young is a devastating complication of inherited heart disorders. Finding the precise cause of death is important, but it is often unresolved after postmortem investigation. The addition of postmortem genetic testing, i.e., the molecular autopsy, can identify additional causes of death. We evaluated DNA extracted from formalin-fixed paraffin-embedded postmortem tissue for exome sequencing-based molecular autopsy after sudden death in the young. We collected clinical and postmortem information from patients with sudden death. Exome sequencing was performed on DNA extracted from fixed postmortem tissue. Variants relevant to the cause of death were sought. Five patients with genetically unresolved sudden death were recruited. DNA extracted from fixed postmortem tissue was degraded. Exome sequencing achieved 20-fold coverage of at least 82% of coding regions. A threefold excess of singleton variants was found in the exome sequencing data of one patient. We found a de novo SCN1A frameshift variant in a patient with sudden unexpected death in epilepsy and a LMNA nonsense variant in a patient with dilated cardiomyopathy. DNA extracted from fixed postmortem tissue is applicable to exome sequencing-based molecular autopsy. Fixed postmortem tissues are an untapped resource for exome-based studies of rare causes of sudden death.Genet Med advance online publication 23 March 2017.
DOI: 10.1038/gim.2017.15
ORCID: 0000-0002-2476-9864
PubMed URL: 28333919
Type: Journal Article
Appears in Collections:Journal articles

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