Genetics and sudden death

Lombardi, Raffaella

doi:10.1097/hco.0b013e32835fb7f3

Cited by 14 publications

(8 citation statements)

References 95 publications

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“…In addition, pathogenic variations in genes encoding structural proteins are responsible for cardiomyopathies (Hypertrophic Cardiomyopathy (HCM), Dilated Cardiomyopathy (DCM), and Arrhythmogenic Cardiomyopathy (AC), among others). These cardiomyopathies will usually present anatomo-morphological changes in the cardiac tissue, which can be diagnosed at autopsy [13], but recent reports have suggested that in infants they could also be potentially responsible for sudden death in the structurally normal heart [14, 15]. …”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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BackgroundSudden 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 FindingsOur 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.ConclusionsCardiac 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.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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“…No mutations were found in the entire coding regions of the major LQTS associated genes (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, and KCNJ2) and in ANK2 and RyR2 genes [3,4]. DNA was submitted to open reading frame/splice site mutational analysis on CAV3 gene by PCR and direct DNA sequencing, using coding region flanking primers (Table 1).…”

Section: Methodsmentioning

confidence: 99%

“…Congenital cardiac channelopathies and cardiomyopathies are known to play significant roles in SCD [2-4]. In the first cases genotype-phenotype correlation studies have identified most of the known disease-causing defects in genes encoding cardiac ion channels or other membrane components [3], while in the second cases cardiac structural abnormalities have been detected in subjects carrying mutations in sarcomeric proteins [4]. However, the identified variants commonly have reduced penetrance and are associated with heterogeneous clinical manifestations [2].…”

Section: Introductionmentioning

confidence: 99%

Identification and functional analysis of a new putative caveolin-3 variant found in a patient with sudden unexplained death

et al. 2014

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BackgroundSudden cardiac death (SCD) is the clinical outcome of a lethal arrhythmia that can develop on the background of unrecognized channelopathies or cardiomyopathies. Several susceptibility genes have been identified for the congenital forms of these cardiac diseases, including caveolin-3 (Cav-3) gene. In the heart Cav-3 is the main component of caveolae, plasma membrane domains that regulate multiple cellular processes highly relevant for cardiac excitability, such as trafficking, calcium homeostasis, signal transduction and cellular response to injury. Here we characterized a new putative Cav-3 variant, Cav-3 V82I, found in a patient with SCD.ResultsIn heterologous systems Cav-3 V82I was expressed at significantly higher level than Cav-3 WT and accumulated within the cells. Cells expressing Cav-3 V82I exhibited a decreased activation of extracellular-signal-regulated kinases (ERKs) and were more vulnerable to sub-lethal osmotic stress.ConclusionConsidering that abnormal loss of myocytes can play a mechanistic role in lethal cardiac diseases, we suggest that the detrimental effect of Cav-3 V82I variant on cell viability may participate in determining the susceptibility to cardiac death.

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“…In contrast to cases of intentional or suspected violent death, in instances when death occurred either suddenly, unexpectedly, or involving infants and the young [3], autopsy sampling focuses on the corpse's own substances to aid in determination of genetic markers and mutations which could be responsible for the cause or manner of death. From this point of view, the use of forensic genetics is not only strictly limited to purposes of identification, but may also be tasked by performing genetic tests for genes associated with disease [190,191]. Several specific or rare diseases may be linked to a particular pathological condition in cases of both positive and negative autopsy [189,192].…”

Section: Markers For Investigation Of Cause or Manner Of Death: Molecmentioning

confidence: 99%

Forensic DNA Technological Advancements as an Emerging Perspective on Medico-Legal Autopsy: A Mini Review

Pádár¹,

Zenke²,

Kozma³

2018

Post Mortem Examination and Autopsy - Current Issues From Death to Laboratory Analysis

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The importance of biological traces and evidences related to a criminal matter has been recognized for a long time. The examination of the expression of genetic polymorphism has been an integral part of the multidisciplinary field of medico-legal autopsy for over a century. Since the initial application of blood group antigens for personalization of a putative perpetrator in a murder case, the discipline of forensic genetics has evolved as a standard of forensic sciences. The real breakthrough, the application of molecular tools and processes for the in-vitro replication of genetic substances, has increasingly allowed the exploitation of advances of molecular genetics for both forensic and criminal investigations. Although there are certainly many more applications and scientific fields in the medico-legal arena, the relatively fast progress of genetics, which has accelerated recently with state-of-art technologies, can provide ever more relevant information in relation to a corpse or the cause and manner that resulted in the corpse for autopsy. This topic concerns the currently accepted forensic DNA technology, and the last section reviews commonly used markers for nuclear and mitochondrial DNA analysis as well as ongoing research. This review also focuses on the increasingly important non-human sources of DNA, and shortly covers the main aspects of animal forensic DNA examination.

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Genetics and sudden death

Cited by 14 publications

References 95 publications

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

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

Identification and functional analysis of a new putative caveolin-3 variant found in a patient with sudden unexplained death

Forensic DNA Technological Advancements as an Emerging Perspective on Medico-Legal Autopsy: A Mini Review

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