Original articleCardiac Channel Molecular Autopsy: Insights From 173 Consecutive Cases of Autopsy-Negative Sudden Unexplained Death Referred for Postmortem Genetic Testing
Section snippets
Medical Examiner–Referred Cases of Autopsy-Negative SUD
From September 1, 1998, through October, 31, 2010, 173 medical examiners' cases of autopsy-negative SUD (106 males; mean ± SD age, 18.4±12.9 years; range, 1-69 years) were referred to Mayo Clinic's Windland Smith Rice Sudden Death Genomics Laboratory for a cardiac channel molecular autopsy. After receipt of written consent from the decedent's appropriate next of kin for this Mayo Foundation Institutional Review Board–approved protocol, a postmortem genetic mutational analysis (ie, cardiac
Cohort Description
Demographic characteristics for this consecutively referred SUD cohort are given in Table 1. Briefly, there were 173 cases (106 males and 67 females; mean ± SD age, 18.4±12.9 years; range, 1-69 years; 89% white). The mean ± SD ages of the males (18.2±13 years; range, 1-69 years) and females (18.8±13 years; range, 1-52 years) were similar. Most (161/173 [93.1%]) were 40 years or younger at their SUD. The circumstance (events or triggers) surrounding the SUD was grouped into 1 of 3 categories,
Discussion
Postmortem genetic testing (the cardiac channel molecular autopsy) has not yet been transformed fully from a research-based effort into a routine, standard part of the conventional autopsy when the coroner, medical examiner, or forensic pathologist is faced with a case of SUD in the young. However, recently, Basso and colleagues,18 on behalf of the Association for European Cardiovascular Pathology, have strongly recommended postmortem genetic analysis in both structural and nonstructural
Conclusion
More than one-fourth of autopsy-negative SUD cases may stem from either LQTS- or CPVT-associated channelopathic mutations. A cardiac channel molecular autopsy should be considered as a standard part of the evaluation of autopsy-negative SUD, especially among children with exercise-induced SUD, adolescent girls, and those with a positive personal or family history of cardiac events. A 2-tiered approach starting with the LQTS-susceptibility genes for female patients with SUD and the CPVT
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2022, Computers in Biology and MedicineCitation Excerpt :Turning points are key nodes that connect two clusters to indicate new research, and key nodes with high centrality of turning points indicate the emergence of new research hotspots. Among the 10 turning point articles, six articles used molecular autopsy for the diagnosis of SUD [3,4,16–19]; three articles studied SUDEP, summarizing and generalizing its risk factors [20–22]; and one article discussed diagnostic guidelines for SIDS [23]. Thus, molecular autopsy techniques accounted for a large proportion of the turning point articles, and the combination of the six molecular autopsy papers dating between 2007 and 2015 suggested that the application of molecular autopsy for the diagnosis of SUD was a research hotspot in the last decade.
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Grant Support: This work was supported by the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program, the Sheikh Zayed Saif Mohammed Al Nahyan Fund in Pediatric Cardiology Research, the Dr. Scholl Fund, the Hannah M. Wernke Memorial Fund, and the National Institutes of Health, grant number HD42569.
Potential Competing Interests: M.J.A. is a consultant for Biotronik, Boston Scientific, Medtronic, St. Jude Medical Inc, and Transgenomic. Intellectual property derived from M.J.A.'s research program resulted in license agreements in 2004 between Mayo Clinic Health Solutions (formerly Mayo Medical Ventures) and PGxHealth (formerly Genaissance Pharmaceuticals, recently acquired by Transgenomic). D.J.T., A.M.-D., M.L.W., and C.M.H. have no conflicts to disclose. M.J.A. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.