Genetic analysis in post-mortem samples with micro-ischemic alterations.

Sudden cardiac arrest is a leading cause of death worldwide. Most cardiac arrests happen in patients who have previously suffered a myocardial infarct. The risk of sudden death after infarction may increase in people who carry a pathogenic genetic alteration in cardiac ion channels. We hypothesized that micro-ischemia could trigger lethal arrhythmogenesis, thus we sought to identify genetic alterations in cardiac ion channels in patients with micro-ischemic disease. We studied a cohort of 56 post-mortem samples. Autopsy studies identified myocardial infarction as the cause of death in each case. We used both Sanger sequencing and next-generation sequencing to screen candidate genes associated with sudden cardiac death. We identified six rare missense genetic variations in five unrelated patients. Two variants have been previously reported; one is associated with atrial fibrillation (SCN5A_p.H445D), and the other is predicted to be benign (ANK2_p.T2059M). The novel variants were predicted in silico as benign, except for one (RyR2_p.M4019T), which was classified as deleterious. Our post-mortem, micro-infarction cohort displayed a rate of nearly 10% non-common genetic variants. However, the clinical significance of most of the identified variants remains unknown due to lack of family assessment. Further analyses should be performed in large cohorts to clarify the role of ion-channel gene analysis in samples showing microscopic ischemic alterations.

Sudden Arrhythmic Death During Exercise: A Post-Mortem Genetic Analysis.

BACKGROUND: Sudden cardiac death is a natural and unexpected death that occurs within 1 h of the first symptom. Most sudden cardiac deaths occur during exercise, mostly as a result of myocardial infarction. After autopsy, some cases, especially in the young, are diagnosed as cardiomyopathies or remain without a conclusive cause of death. In both situations, genetic alterations may explain the arrhythmia. OBJECTIVE: Our aim was to identify a genetic predisposition to sudden cardiac death in a cohort of post-mortem cases of individuals who died during exercise, with a structurally normal heart, and were classified as arrhythmogenic death. METHODS: We analyzed a cohort of 52 post-mortem samples from individuals <50 years old who had a negative autopsy. Next-generation sequencing technology was used to screen genes associated with sudden cardiac death. RESULTS: Our cohort showed a male prevalence (12:1). Half of the deaths occurred in individuals 41-50 years of age. Running was the most common exercise activity during the fatal event, accounting for 46.15% of cases. Genetic analysis identified 83 rare variants in 37 samples (71.15% of all samples). Of all rare variants, 36.14% were classified as deleterious, being present in 53.84% of all cases. CONCLUSIONS: A comprehensive analysis of sudden cardiac death-related genes in individuals who died suddenly while exercising enabled the identification of potentially causative variants. However, many genetic variants remain of indeterminate significance, thus further work is needed before clinical translation. Nonetheless, comprehensive genetic analysis of individuals who died during exercise enables the detection of potentially causative variants and helps to identify at-risk relatives.

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

[This corrects the article DOI: 10.1371/journal.pone.0167358.].

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

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.

[Differences between immediate and 30-day deaths due to traffic injuries according to forensic sources]. / Diferencias entre fallecimientos inmediatos y a 30 días por lesiones por tráfico según fuentes forenses.

OBJECTIVE: To study immediate (same day of the collision) and delayed (within 30 days of the collision) deaths due to traffic injuries in Catalonia (Spain) according to forensic sources and to assess the differences between the two kinds of deaths. MATERIAL AND METHODS: An observational study was conducted of all the traffic accident deaths registered in the Institute of Legal Medicine of Catalonia between January 1(st) 2005 and December 31(st) 2014. Data analysis was performed using the SPSS v.18.0 statistical package. Comparisons of proportions were based on the χ(2) test. RESULTS: During the study period, 4044 deaths due to traffic injuries were recorded. Deaths within 30 days included more women, minors, elderly people, and pedestrians than immediate deaths. CONCLUSIONS: Traffic injury deaths in the 30 days following a crash differ from immediate deaths.

A body, a dog, and a fistful of scats.

Dogs and coyotes are the most frequently reported canids responsible for scavenging human remains. We present the case of a 90-year-old woman whose mummified body was found in her home showing partial destruction of the thorax and extremities and absence of the cranium. The victim lived with a beagle dog whose dead body was also found, along with abundant scats throughout the house. Scavenging by the decedent's pet was the proposed hypothesis for the partial dismemberment and consumption of her body. Forensic analysis revealed that the victim died as a result of an accidental fracture of the proximal femoral epiphysis. Bone exam showed signs of canine scavenging on certain bones. Macroscopic and histological analyses of the dog feces revealed the presence of small bone fragments within scats. All the collected data supported the hypothesis that the decedent's pet fed on the victim following her death. The current case illustrates that forensic anthropology has much more to offer than personal identification and determining the manner of death. Systematic search and examination of scat deposits recovered from the scene may be very useful in the medicolegal investigation, identifying the origin of body mutilation and particularly the animal responsible for any scavenging.

Post-mortem genetic analysis in juvenile cases of sudden cardiac death.

BACKGROUND: The reason behind a sudden death of a young individual remains unknown in up to 50% of postmortem cases. Pathogenic mutations in genes encoding heart proteins are known to cause sudden cardiac death. OBJECTIVE: The aim of our study was to ascertain whether genetic alterations could provide an explanation for sudden cardiac death in a juvenile cohort with no-conclusive cause of death after comprehensive autopsy. METHODS: Twenty-nine cases <15 years showing no-conclusive cause of death after a complete autopsy were studied. Genetic analysis of 7 main genes associated with sudden cardiac death was performed using Sanger technology in low quality DNA cases, while in good quality cases the analysis of 55 genes associated with sudden cardiac death was performed using Next Generation Sequencing technology. RESULTS: Thirty-five genetic variants were identified in 12 cases (41.37%). Ten genetic/variants in genes encoding cardiac ion channels were identified in 8 cases (27.58%). We also identified 9 cases (31.03%) carrying 25 genetic variants in genes encoding structural cardiac proteins. Nine cases carried more than one genetic variation, 5 of them combining structural and non-structural genes. CONCLUSIONS: Our study supports the inclusion of molecular autopsy in forensic routine protocols when no conclusive cause of death is identified. Around 40% of sudden cardiac death young cases carry a genetic variant that could provide an explanation for the cause of death. Because relatives could be at risk of sudden cardiac death, our data reinforce their need of clinical assessment and, if indicated, of genetic analysis.

A proposed dissection procedure for vertebral arteries in forensic pathology.

Vertebral artery removing constitutes a significant forensic pathology challenge. Dissection techniques during head-neck autopsy are based on anterior approach, a difficult method, which is unable to assess the transverse part of the artery. This work presents an original and simple method for dissecting vertebral arteries by a posterior approach, opening the vertebroarterial canal through the spinal canal without any special equipment. Once the spinal cord is removed, the transversarium foramens are opened by an internal cut at the pedicle and an external cut at the transverse process. This enables us to visualize vertebral arteries in its entirety. The method improves both the examination of the upper extracranial segment of the vertebral artery and the neuropathological study when arterial injury is suspected. Applying this method routinely is both feasible and useful in suspected cases of vertebral artery trauma and could contribute to assess more precisely the actual incidence of this injury.

Traumatic bilateral vertebral artery dissection.

Traumatic vertebral artery dissection is not often seen by forensic pathologists, and cases investigated are scarce in the forensic literature. We present the case of a 40-year-old woman cyclist who was struck by a car while wearing a helmet, and was neurologically near normal immediately thereafter at Emergency. She presented 48 h later with acute right hemiparesis, decreasing level of consciousness, and unsteadiness. CT revealed massive cerebellar infarction. CT angiography was normal. The patient died in coma 7 days after injury and autopsy revealed bilateral edematous cerebellar infarction and bilateral vertebral artery dissection. Rotational neck injury and mural tear in the wall of the Atlantic parts of both vertebral arteries is suggested as the possible mechanism of the arterial injury. Head and neck injuries are reported as a precipitating cause of vertebral artery injury. The possible influence of trauma may be further underestimated if longer intervals between vessel dissection and ischemia occur. The current case illustrates that "talk-and-die" syndrome may be due to occult vertebral artery dissection, possibly bilateral. In forensic cases of delayed death after mild trauma to the head and neck, the vertebral arteries should be examined for the cause of death.