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      Molecular autopsy for sudden death in Japan

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          Abstract

          Japan has various death investigation systems; however, external examinations, postmortem computed tomography, macroscopic examinations, and microscopic examinations are performed regardless of the system used. These examinations can reveal morphological abnormalities, whereas the cause of death in cases with non-morphological abnormalities can be detected through additional examinations. Molecular autopsy and postmortem genetic analyses are important additional examinations. They are capable of detecting inherited arrhythmias or inherited metabolic diseases, which are representative non-morphological disorders that cause sudden death, especially in infants and young people. In this review, we introduce molecular autopsy reports from Japan and describe our experience with representative cases. The relationships between drug-related deaths and genetic variants are also reviewed. Based on the presented information, molecular autopsy is expected to be used as routine examinations in death investigations because they can provide information to save new lives.

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          Most cited references93

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          RBM20, a gene for hereditary cardiomyopathy, regulates titin splicing.

          Alternative splicing has a major role in cardiac adaptive responses, as exemplified by the isoform switch of the sarcomeric protein titin, which adjusts ventricular filling. By positional cloning using a previously characterized rat strain with altered titin mRNA splicing, we identified a loss-of-function mutation in the gene encoding RNA binding motif protein 20 (Rbm20) as the underlying cause of pathological titin isoform expression. The phenotype of Rbm20-deficient rats resembled the pathology seen in individuals with dilated cardiomyopathy caused by RBM20 mutations. Deep sequencing of the human and rat cardiac transcriptome revealed an RBM20-dependent regulation of alternative splicing. In addition to titin (TTN), we identified a set of 30 genes with conserved splicing regulation between humans and rats. This network is enriched for genes that have previously been linked to cardiomyopathy, ion homeostasis and sarcomere biology. Our studies emphasize the key role of post-transcriptional regulation in cardiac function and provide mechanistic insights into the pathogenesis of human heart failure.
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            A Prospective Study of Sudden Cardiac Death among Children and Young Adults

            Sudden cardiac death among children and young adults is a devastating event. We performed a prospective, population-based, clinical and genetic study of sudden cardiac death among children and young adults.
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              HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA).

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                Author and article information

                Journal
                J Toxicol Pathol
                J Toxicol Pathol
                TOX
                Journal of Toxicologic Pathology
                Japanese Society of Toxicologic Pathology
                0914-9198
                1881-915X
                30 August 2023
                January 2024
                : 37
                : 1
                : 1-10
                Affiliations
                [1 ]Department of Legal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya-shi, Hyogo 663-8501, Japan
                [2 ]Department of Legal Medicine, Kansai Medical University, 2-5-1 Shinmachi, Hirakata-shi, Osaka 573-1010, Japan
                [3 ]Division of Forensic Pathology and Science, Department of Medical and Dental Sciences, Graduate School of Biomedical Sciences, School of Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki-shi, Nagasaki 852-8523, Japan
                [4 ]Department of Forensic Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu-shi, Fukuoka 807-8555, Japan
                Author notes
                *Corresponding author: T Yamamoto (e-mail: tk-yamamoto@ 123456hyo-med.ac.jp )
                Article
                2023-0080
                10.1293/tox.2023-0080
                10811381
                38283375
                b51079a5-e57a-4329-bb99-faf47449449c
                ©2024 The Japanese Society of Toxicologic Pathology

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. (CC-BY-NC-ND 4.0: https://creativecommons.org/licenses/by-nc-nd/4.0/ ).

                History
                : 21 June 2023
                : 17 August 2023
                Categories
                Featured Article: Explore cause of death —human and animals— Invited Review

                Pathology
                forensic autopsy,metabolic autopsy,molecular autopsy,postmortem genetic analysis,sudden death

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