Hyper-SUMOylation of K+ Channels in Sudden Unexplained Death in Epilepsy: Isolation and Primary Culture of Dissociated Hippocampal Neurons from Newborn Mice for Subcellular Localization

2017 ◽  
pp. 63-71 ◽  
Author(s):  
Xu Chen ◽  
Shanshan Zhang ◽  
Jifang Huang ◽  
Wanying Dong ◽  
Hui Xiao ◽  
...  
Keyword(s):  
Subcellular Localization ◽  
Primary Culture ◽  
Hippocampal Neurons ◽  
Newborn Mice ◽  
K Channels ◽  
Sudden Unexplained Death ◽  
Unexplained Death

scholarly journals Differential Methylation in the GSTT1 Regulatory Region in Sudden Unexplained Death and Sudden Unexpected Death in Epilepsy

2021 ◽  
Vol 22 (6) ◽  
pp. 2790
Author(s):  
Steffan Noe Christiansen ◽  
Stine Bøttcher Jacobsen ◽  
Jeppe Dyrberg Andersen ◽  
Marie-Louise Kampmann ◽  
Linea Christine Trudsø ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cardiac Tissue ◽  
Heart Diseases ◽  
Regulatory Region ◽  
Differential Methylation ◽  
Sudden Unexpected Death ◽  
Diagnostic Challenge ◽  
Unexpected Death ◽  
Sudden Unexplained Death ◽  
Unexplained Death

Sudden cardiac death (SCD) is a diagnostic challenge in forensic medicine. In a relatively large proportion of the SCDs, the deaths remain unexplained after autopsy. This challenge is likely caused by unknown disease mechanisms. Changes in DNA methylation have been associated with several heart diseases, but the role of DNA methylation in SCD is unknown. In this study, we investigated DNA methylation in two SCD subtypes, sudden unexplained death (SUD) and sudden unexpected death in epilepsy (SUDEP). We assessed DNA methylation of more than 850,000 positions in cardiac tissue from nine SUD and 14 SUDEP cases using the Illumina Infinium MethylationEPIC BeadChip. In total, six differently methylated regions (DMRs) between the SUD and SUDEP cases were identified. The DMRs were located in proximity to or overlapping genes encoding proteins that are a part of the glutathione S-transferase (GST) superfamily. Whole genome sequencing (WGS) showed that the DNA methylation alterations were not caused by genetic changes, while whole transcriptome sequencing (WTS) showed that DNA methylation was associated with expression levels of the GSTT1 gene. In conclusion, our results indicate that cardiac DNA methylation is similar in SUD and SUDEP, but with regional differential methylation in proximity to GST genes.

scholarly journals Re-evaluation of single nucleotide variants and identification of structural variants in a cohort of 45 sudden unexplained death cases

2021 ◽  
Author(s):  
Jacqueline Neubauer ◽  
Shouyu Wang ◽  
Giancarlo Russo ◽  
Cordula Haas
Keyword(s):  
Sudden Death ◽  
Cardiac Diseases ◽  
Structural Variants ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Sudden Unexplained Death ◽  
Unexplained Death ◽  
Pathogenic Variants ◽  
The Impact ◽  
Death Cases

AbstractSudden unexplained death (SUD) takes up a considerable part in overall sudden death cases, especially in adolescents and young adults. During the past decade, many channelopathy- and cardiomyopathy-associated single nucleotide variants (SNVs) have been identified in SUD studies by means of postmortem molecular autopsy, yet the number of cases that remain inconclusive is still high. Recent studies had suggested that structural variants (SVs) might play an important role in SUD, but there is no consensus on the impact of SVs on inherited cardiac diseases. In this study, we searched for potentially pathogenic SVs in 244 genes associated with cardiac diseases. Whole-exome sequencing and appropriate data analysis were performed in 45 SUD cases. Re-analysis of the exome data according to the current ACMG guidelines identified 14 pathogenic or likely pathogenic variants in 10 (22.2%) out of the 45 SUD cases, whereof 2 (4.4%) individuals had variants with likely functional effects in the channelopathy-associated genes SCN5A and TRDN and 1 (2.2%) individual in the cardiomyopathy-associated gene DTNA. In addition, 18 structural variants (SVs) were identified in 15 out of the 45 individuals. Two SVs with likely functional impairment were found in the coding regions of PDSS2 and TRPM4 in 2 SUD cases (4.4%). Both were identified as heterozygous deletions, which were confirmed by multiplex ligation-dependent probe amplification. In conclusion, our findings support that SVs could contribute to the pathology of the sudden death event in some of the cases and therefore should be investigated on a routine basis in suspected SUD cases.

scholarly journals Sudden Unexplained Death

Circulation ◽  
2005 ◽  
Vol 112 (2) ◽  
pp. 207-213 ◽  
Author(s):  
Hanno L. Tan ◽  
Nynke Hofman ◽  
Irene M. van Langen ◽  
Allard C. van der Wal ◽  
Arthur A.M. Wilde
Keyword(s):  
Sudden Unexplained Death ◽  
Unexplained Death

scholarly journals Minimally invasive autopsy for fetuses and children based on a combination of post-mortem MRI and endoscopic examination: a feasibility study

2019 ◽  
Vol 23 (46) ◽  
pp. 1-104 ◽  
Author(s):  
Celine Lewis ◽  
John C Hutchinson ◽  
Megan Riddington ◽  
Melissa Hill ◽  
Owen J Arthurs ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Cause Of Death ◽  
Clinical Indication ◽  
Religious Leaders ◽  
Training Requirements ◽  
Less Invasive ◽  
Sudden Unexplained Death ◽  
Unexplained Death ◽  
Minimally Invasive Autopsy ◽  
Autopsy Data

BackgroundLess invasive perinatal and paediatric autopsy methods, such as imaging alongside targeted endoscopy and organ biopsy, may address declining consent rates for traditional autopsy, but their acceptability and accuracy are not known.ObjectivesThe aims of this study were to provide empirical data on the acceptability and likely uptake for different types of autopsy among key stakeholders (study 1); and to analyse existing autopsy data sources to provide estimates of the potential efficacy of less invasive autopsy (LIA) and its projected utility in clinical practice (study 2).Review methodsStudy 1: this was a mixed-methods study. Parents were involved in research design and interpretation of findings. Substudy 1: a cross-sectional survey of 859 parents who had experienced miscarriage, termination of pregnancy for fetal anomaly, stillbirth, infant or child death, and interviews with 20 responders. Substudy 2: interviews with 25 health professionals and four coroners. Substudy 3: interviews with 16 religious leaders and eight focus groups, with 76 members of the Muslim and Jewish community. Study 2: a retrospective analysis of national data in addition to detailed information from an existing in-house autopsy database of > 5000 clinical cases that had undergone standard autopsy to determine the proportion of cases by clinical indication group for which tissue sampling of specific internal organs significantly contributed to the diagnosis.ResultsSubstudy 1: 91% of participants indicated that they would consent to some form of LIA, 54% would consent to standard autopsy, 74% to minimally invasive autopsy (MIA) and 77% to non-invasive autopsy (NIA). Substudy 2: participants viewed LIA as a positive development, but had concerns around the limitations of the technology and de-skilling the workforce. Cost implications, skills and training requirements were identified as implementation challenges. Substudy 3: religious leaders agreed that NIA was religiously permissible, but MIA was considered less acceptable. Community members indicated that they might consent to NIA if the body could be returned for burial within 24 hours. Study 2: in 5–10% of cases of sudden unexplained death in childhood and sudden unexplained death in infants, the final cause of death is determined by routine histological sampling of macroscopically normal organs, predominantly the heart and lungs, and in this group routine histological sampling therefore remains an important aspect of investigation. In contrast, routine histological examination of macroscopically normal organs rarely (< 0.5%) provides the cause of death in fetal cases, making LIA and NIA approaches potentially highly applicable.LimitationsA key limitation of the empirical research is that it is hypothetical. Further research is required to determine actual uptake. Furthermore, because of the retrospective nature of the autopsy data set, findings regarding the likely contribution of organ sampling to final diagnosis are based on extrapolation of findings from historical autopsies, and prospective data collection is required to validate the conclusions.ConclusionsLIA is viable and acceptable (except for unexplained deaths), and likely to increase uptake. Further health economic, performance and implementation studies are required to determine the optimal service configuration required to offer this as routine clinical care.FundingThe National Institute for Health Research Health Technology Assessment programme.

scholarly journals Sudden unexplained death in adults caused by intracranial pathology

2002 ◽  
Vol 55 (1) ◽  
pp. 44-50 ◽  
Author(s):  
M Black ◽  
D I Graham
Keyword(s):  
Sudden Unexplained Death ◽  
Unexplained Death
Sign in / Sign up

Export Citation Format

Share Document