The ethics of conducting molecular autopsies in cases of sudden death in the young

McGuire, Amy L.; Moore, Quianta; Majumder, Mary A.; Walkiewicz, Magdalena; Eng, Christine M.; Belmont, John W.; Nassef, Salma; Darilek, Sandra; Rutherford, Katie; Pereira, Stacey; Scherer, Steven E.; Sutton, V. Reid; Wolf, Dwayne A.; Gibbs, Richard A.; Kahn, Roger; Sánchez, Luis A.

doi:10.1101/gr.192401.115

Cited by 18 publications

(19 citation statements)

References 23 publications

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“…Many of the underlying causes of SDY are hereditary, thus, a postmortem genetic diagnosis [molecular autopsy (MA)] provides a landmark for both the identification of the cause of death and a potential resolution of the uncertainty for risk to living relatives ( 8 – 13 ). In this regard, minimally invasive molecular tests, enabled by recent technological advances in high-throughput DNA sequencing, have reduced the cost of genomic sequencing relative to the gene panel-based tests traditionally available to medical examiners ( 14 – 17 ).…”

Section: Introductionmentioning

confidence: 99%

Molecular Autopsy for Sudden Death in the Young: Is Data Aggregation the Key?

Rueda

Wagner

Phillips

et al. 2017

Front. Cardiovasc. Med.

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The Scripps molecular autopsy study seeks to incorporate genetic testing into the postmortem examination of cases of sudden death in the young (<45 years old). Here, we describe the results from the first 2 years of the study, which consisted of whole exome sequencing (WES) of a cohort of 50 cases predominantly from San Diego County. Apart from the individual description of cases, we analyzed the data at the cohort-level, which brought new perspectives on the genetic causes of sudden death. We investigated the advantages and disadvantages of using WES compared to a gene panel for cardiac disease (usually the first genetic test used by medical examiners). In an attempt to connect complex clinical phenotypes with genotypes, we classified samples by their genetic fingerprint. Finally, we studied the benefits of analyzing the mitochondrial DNA genome. In this regard, we found that half of the cases clinically diagnosed as sudden infant death syndrome had an increased ratio of heteroplasmic variants, and that the variants were also present in the mothers. We believe that community-based data aggregation and sharing will eventually lead to an improved classification of variants. Allele frequencies for the all cases can be accessed via our genomics browser at .

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Section: Introductionmentioning

confidence: 99%

Molecular Autopsy for Sudden Death in the Young: Is Data Aggregation the Key?

Rueda

Wagner

Phillips

et al. 2017

Front. Cardiovasc. Med.

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“…Therefore, molecular autopsy programs are best served by the inclusion of experts in biomedical ethics and genetic counselors on review boards. For this study, a consortium of clinical and genetic experts from the Harris County Institute of Forensic Sciences and Baylor College of Medicine collaborated with the Baylor College of Medicine Center for Medical Ethics and Health Policy and genetic counselors to establish guidelines on the disclosure of genetic information (McGuire et al 2016). The results of these molecular autopsies are envisioned to become part of the normal medicolegal death investigation and will, in some instances, result in amendments of autopsy reports and death certificates.…”

Section: Discussionmentioning

confidence: 99%

Postmortem genetic screening for the identification, verification, and reporting of genetic variants contributing to the sudden death of the young

et al. 2016

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Each year in the United States, thousands of cases of sudden and unexpected deaths of infants, children, and young adults are assigned an undetermined cause of death after postmortem investigation and autopsy. Heritable genetic variants have been suggested as the cause of up to a third of sudden death (SD) cases. Elucidation of the genetic variants involved in SD cases is important to not only help establish cause and manner of death of these individuals, but to also aid in determining whether familial genetic testing should be considered. Previously, these types of postmortem screenings have not been a feasible option for most county medical examiners' and coroners' offices. We sequenced full exons of 64 genes associated with SD in the largest known cohort (351) of infant and young SD decedents using massively parallel sequencing at <$600 per sample. Genetic variants were assessed through literature review and clinical evaluation by a multidisciplinary consortium of experts. Thirteen individuals (3.7%), eight infants (2.8% of those <1 yr of age) and five children/young adults (7.0% of those >1 yr of age), were found to have a reportable genetic variant contributing to SD. These percentages represent an estimate lower than those previously reported. Overall yields and results likely vary between studies due to differences in evaluation techniques and reporting. Additionally, we recommend ongoing assessment of data, including nonreported novel variants, as technology and literature continually advance. This study demonstrates a strategy to implement molecular autopsies in medicolegal investigations of young SD decedents.

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“…Many forensic centers lack sufficient multidisciplinary teams to counsel families and conduct research studies. There are also substantial legal and procedural barriers to molecular autopsy studies, which may vary according to jurisdiction (McGuire et al, 2016). Individuals who die out of the hospital are even less likely to receive a complete or molecular autopsy.…”

Section: Definition and Backgroundmentioning

confidence: 99%

“Donating our bodies to science”: A discussion about autopsy and organ donation in Turner syndrome

Prakash¹,

Roman

Crenshaw

et al. 2019

American J of Med Genetics Pt C

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At the Third Turner Resource Network Symposium, a working group presented the results of collaborative discussions about the importance of autopsy in Turner syndrome (TS). Considerable gaps in understanding the causes of death in TS can only be closed by more frequent death investigations and autopsies. The presentation included an overview of autopsy methods, strategies for utilizing autopsy, and biobanking to address research questions about TS, and the role of palliative care in the context of autopsy. This review highlights strategies to promote autopsy and tissue donation, culminating with an action plan to increase autopsy rates in the TS community.

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The ethics of conducting molecular autopsies in cases of sudden death in the young

Cited by 18 publications

References 23 publications

Molecular Autopsy for Sudden Death in the Young: Is Data Aggregation the Key?

Molecular Autopsy for Sudden Death in the Young: Is Data Aggregation the Key?

Postmortem genetic screening for the identification, verification, and reporting of genetic variants contributing to the sudden death of the young

“Donating our bodies to science”: A discussion about autopsy and organ donation in Turner syndrome

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