Dataset Information

Natural and Undetermined Sudden Death: Value of Post-Mortem Genetic Investigation.

ABSTRACT:

Background

Sudden unexplained death may be the first manifestation of an unknown inherited cardiac disease. Current genetic technologies may enable the unraveling of an etiology and the identification of relatives at risk. The aim of our study was to define the etiology of natural deaths, younger than 50 years of age, and to investigate whether genetic defects associated with cardiac diseases could provide a potential etiology for the unexplained cases.

Methods and findings

Our cohort included a total of 789 consecutive cases (77.19% males) <50 years old (average 38.6±12.2 years old) who died suddenly from non-violent causes. A comprehensive autopsy was performed according to current forensic guidelines. During autopsy a cause of death was identified in most cases (81.1%), mainly due to cardiac alterations (56.87%). In unexplained cases, genetic analysis of the main genes associated with sudden cardiac death was performed using Next Generation Sequencing technology. Genetic analysis was performed in suspected inherited diseases (cardiomyopathy) and in unexplained death, with identification of potentially pathogenic variants in nearly 50% and 40% of samples, respectively.

Conclusions

Cardiac disease is the most important cause of sudden death, especially after the age of 40. Close to 10% of cases may remain unexplained after a complete autopsy investigation. Molecular autopsy may provide an explanation for a significant part of these unexplained cases. Identification of genetic variations enables genetic counseling and undertaking of preventive measures in relatives at risk.

SUBMITTER: Sanchez O

PROVIDER: S-EPMC5145162 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Natural and Undetermined Sudden Death: Value of Post-Mortem Genetic Investigation.

Sanchez Olallo O Campuzano Oscar O Fernández-Falgueras Anna A Sarquella-Brugada Georgia G Cesar Sergi S Mademont Irene I Mates Jesus J Pérez-Serra Alexandra A Coll Monica M Pico Ferran F Iglesias Anna A Tirón Coloma C Allegue Catarina C Carro Esther E Gallego María Ángeles MÁ Ferrer-Costa Carles C Hospital Anna A Bardalet Narcís N Borondo Juan Carlos JC Vingut Albert A Arbelo Elena E Brugada Josep J Castellà Josep J Medallo Jordi J Brugada Ramon R

PloS one 20161208 12

<h4>Background</h4>Sudden unexplained death may be the first manifestation of an unknown inherited cardiac disease. Current genetic technologies may enable the unraveling of an etiology and the identification of relatives at risk. The aim of our study was to define the etiology of natural deaths, younger than 50 years of age, and to investigate whether genetic defects associated with cardiac diseases could provide a potential etiology for the unexplained cases.<h4>Methods and findings</h4>Our co ...[more]

PMID: 27930701

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Project description:IntroductionDue to its peculiar anatomy and physiology, the pericardial fluid is a biological matrix of particular interest in the forensic field. Despite this, the available literature has mainly focused on post-mortem biochemistry and forensic toxicology, while to the best of authors' knowledge post-mortem metabolomics has never been applied. Similarly, estimation of the time since death or post-mortem interval based on pericardial fluids has still rarely been attempted.ObjectivesWe applied a metabolomic approach based on 1H nuclear magnetic resonance spectroscopy to ascertain the feasibility of monitoring post-mortem metabolite changes on human pericardial fluids with the aim of building a multivariate regression model for post-mortem interval estimation.MethodsPericardial fluid samples were collected in 24 consecutive judicial autopsies, in a time frame ranging from 16 to 170 h after death. The only exclusion criterion was the quantitative and/or qualitative alteration of the sample. Two different extraction protocols were applied for low molecular weight metabolites selection, namely ultrafiltration and liquid-liquid extraction. Our metabolomic approach was based on the use of 1H nuclear magnetic resonance and multivariate statistical data analysis.ResultsThe pericardial fluid samples treated with the two experimental protocols did not show significant differences in the distribution of the metabolites detected. A post-mortem interval estimation model based on 18 pericardial fluid samples was validated with an independent set of 6 samples, giving a prediction error of 33-34 h depending on the experimental protocol used. By narrowing the window to post-mortem intervals below 100 h, the prediction power of the model was significantly improved with an error of 13-15 h depending on the extraction protocol. Choline, glycine, ethanolamine, and hypoxanthine were the most relevant metabolites in the prediction model.ConclusionThe present study, although preliminary, shows that PF samples collected from a real forensic scenario represent a biofluid of interest for post-mortem metabolomics, with particular regard to the estimation of the time since death.

Dataset Information

Natural and Undetermined Sudden Death: Value of Post-Mortem Genetic Investigation.

Background

Methods and findings

Conclusions

Publications

Natural and Undetermined Sudden Death: Value of Post-Mortem Genetic Investigation.

Similar Datasets

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