The importance of molecular autopsy in forensic medicine
Authors:
Jana Orlíčková 1; Martin Zeman 2; Tomáš Vojtíšek 2; Ondřej Slabý 1,3
Authors‘ workplace:
Středoevropský technologický institut, Masarykova univerzita, Brno
1; Ústav soudního lékařství LF MU a FN u sv. Anny, Brno
2; Biologický ústav LF MU, Brno
3
Published in:
Čas. Lék. čes. 2022; 161: 207-211
Category:
Review Article
Overview
Standard autopsy does not always detect a cause of individual’s death. It occurs often in cases of sudden death. The reason for decease, at least in a part of unsolved cases, can be revealed using methods of molecular biology and genetics. This approach is called molecular autopsy.
First application dates to the end of 20th century when cause of sudden unexplained death of a young woman was provided only after execution of molecular autopsy. Molecular autopsy (also known as post-mortem genetic testing) finds its application particularly in cases of sudden death of young people or infants as their decease is more frequently associated with hereditary diseases linked for example to heart or metabolic conditions. In terms of methodical development, the form of molecular testing has been improved until now. Originally, targeted analysis of small number of genes was used. Nowadays, whole-exome and whole-genome sequencing slowly becomes a new standard for molecular autopsy. Although molecular autopsy has a potential to be integrated into an autopsy as a standard part of it, for now it has not become a standardised routine part of forensic autopsy.
Keywords:
molecular autopsy – sudden infant death syndrome – sudden death
Sources
1. Edwards WD, Ackerman MJ. Molecular autopsy vs postmortem genetic testing [3] (multiple letters). Mayo Clin Proc 2005; 80: 1234–1235.
2. Ackerman MJ. Molecular Autopsy vs postmortem genetic testing: in response. Mayo Clin Proc 2005; 80: 1235–1236.
3. Ackerman MJ, Tester DJ, Porter BJ, Edwards WD. Molecular diagnosis of the inherited long-QT syndrome in a woman who died after near-drowning. N Engl J Med 1999; 341: 1121–1125.
4. Ahrendsen JT, Filbin MG, Chi SN et al. Increasing value of autopsies in patients with brain tumors in the molecular era. J Neurooncol 2019; 145: 349–355.
5. Simon CT, Skala SL, Killen PD et al. Plasmacytoid urothelial carcinoma: a rapid autopsy case report with unique clinicopathologic and genomic profile. Diagn Pathol 2019; 14: 113.
6. Ahrendsen JT, Torre M, Meredith DM et al. IDH-mutant gliomas with additional class-defining molecular events. Mod Pathol 2021; 34: 1236–1244.
7. Lee HCH, Lai CK, Siu TS et al. Role of postmortem genetic testing demonstrated in a case of glutaric aciduria type II. Diagn Mol Pathol 2010; 19: 184–186.
8. Maiese A, Scatena A, Costantino A et al. MicroRNAs as useful tools to estimate time since death. A systematic review of current literature. Diagnostics 2021; 11: 64.
9. Scrivano S, Sanavio M, Tozzo P, Caenazzo L. Analysis of RNA in the estimation of post-mortem interval: a review of current evidence. Int J Legal Med 2019; 133: 1629–1640.
10. Bayés de Luna A, Elosua R. Sudden Death. Rev Española Cardiol 2012; 65: 1039–1052.
11. Zeman M, Sepši M, Vojtíšek T, Sindler M. Suddenly deceased young individuals autopsied at the Department of forensic medicine, Brno – analysis. Česko-slovenská patologie a Soudní lékařství 2012; 48/57: 44–47.
12. Campuzano O, Allegue C, Partemi S et al. Negative autopsy and sudden cardiac death. Int J Legal Med 2014; 128: 599–606.
13. Iglesias M, Ripoll-Vera T, Perez-Luengo C et al. Diagnostic yield of genetic testing in sudden cardiac death with autopsy findings of uncertain significance. J Clin Med 2021; 10: 1806.
14. Drory Y, Turetz Y, Hiss Y et al. Sudden unexpected death in persons <40 years of age. Am J Cardiol 1991; 68: 1388–1392.
15. Splawski I, Shen J, Timothy KW et al. Spectrum of mutations in Long-QT Syndrome genes: KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation 2000; 102: 1178–1185.
16. Bezzina CR, Lahrouchi N, Priori SG. Genetics of sudden cardiac death. Circ Res 2015; 116: 1919–1936.
17. Bagnall RD, Das K J, Duflou J, Semsarian C. Exome analysis-based molecular autopsy in cases of sudden unexplained death in the young. Hear Rhythm 2014; 11: 655–662.
18. Neubauer J, Lecca MR, Russo G et al. Post-mortem whole-exome analysis in a large sudden infant death syndrome cohort with a focus on cardiovascular and metabolic genetic diseases. Eur J Hum Genet 2017; 25: 404–409.
19. Battelle Insider. MPS vs. NGS: What’s the difference. Inside Battelle, 2017. Dostupné na: http://inside.battelle.org/home/mps-vs.-ngs-what's-the-difference
20. Slabý O. Precizní medicína v onkologii. 1. část: Technologie genomového sekvenování pro účely precizní onkologie. proLékaře.cz, 2019. Dostupné na: www.prolekare.cz/kreditovane-kurzy/precizni-medicina-v-onkologii-109447/technologie-genomoveho-sekvenovani-pro-ucely-precizni-onkologie
21. Kofanova O, Bellora C, Garcia Frasquilho S et al. Standardization of the preanalytical phase of DNA extraction from fixed tissue for next-generation sequencing analyses. N Biotechnol 2020; 54: 52–61.
22. Wong CX, Brown A, Lau DH et al. Epidemiology of sudden cardiac death: global and regional perspectives. Hear Lung Circ 2019; 28: 6–14.
23. Bagnall RD, Weintraub RG, Ingles J et al. A Prospective study of sudden cardiac death among children and young adults. N Engl J Med 2016; 374: 2441–2452.
24. WHO. European Mortality Database (1980–2020). Dostupné na: https://gateway.euro.who.int/en/datasets/european-mortality-database
25. Campuzano O, Sanchez-Molero O, Mademont-Soler I et al. Rare titin (TTN) variants in diseases associated with sudden cardiac death. Int J Mol Sci 2015; 16: 25773–82577.
26. Mak CM, Mok NS, Shum HC et al. Sudden arrhythmia death syndrome in young victims: A five-year retrospective review and two-year prospective molecular autopsy study by next-generation sequencing and clinical evaluation of their first-degree relatives. Hong Kong Med J 2019; 25: 21–29.
27. Giudicessi RJ, Ackerman MJ, Fatkin D, Kovacic JC. Precision medicine approaches to cardiac arrhythmias. J Am Coll Cardiol 2021; 77: 2573–2591.
28. Eurostat. Infant mortality sharply declined over the past decades. 2021. Dostupné na: https://ec.europa.eu/eurostat/web/products-eurostat-news/-/ddn-20210604-1
29. Český statistický úřad. Pohyb obyvatelstva – rok 2019. Dostupné na: www.czso.cz/csu/czso/cri/pohyb-obyvatelstva-rok-2019
30. Fleming PJ, Blair PS, Pease A. Sudden unexpected death in infancy: aetiology, pathophysiology, epidemiology and prevention in 2015. Arch Dis Child 2015; 100: 984–948.
31. Perrone S, Lembo C, Moretti S et al. Sudden infant death syndrome: beyond risk factors. Life 2021; 11: 184.
32. de Visme S, Chalumeau M, Levieux K et al. National variations in recent trends of sudden unexpected infant death rate in western Europe. J Pediatr 2020; 226: 179–185.e4.
33. Goldwater PN. Sudden infant death syndrome, infection, prone sleep position, and vagal neuroimmunology. Front Pediatr 2017; 5: 223
34. Rognum TO, Saugstad OD. Biochemical and immunological studies in SIDS victims. Clues to understanding the death mechanism. Acta Paediatr 1993; 389 (Suppl.): 82–85.
35. Johannsen EB, Baughn LB, Sharma N et al. The genetics of sudden infant death syndrome – towards a gene reference resource. Genes (Basel) 2021; 12: 216.
36. Filonzi L, Magnani C, Lavezzi AM et al. Detoxification genes polymorphisms in SIDS exposed to tobacco smoke. Gene 2018; 648: 1–4.
37. Keywan C, Poduri AH, Goldstein RD, Holm IA. Genetic factors underlying sudden infant death syndrome. Appl Clin Genet 2021; 14: 61–76.
38. Naeye RL. Brain-stem and adrenal abnormalities in the sudden-infant-death syndrome. Am J Clin Pathol 1976; 66: 526–530.
39. Fellmann F, van El CG, Charron P et al. European recommendations integrating genetic testing into multidisciplinary management of sudden cardiac death. Eur J Hum Genet 2019; 27: 1763–1773.
40. Andersen JD, Jacobsen SB, Trudsø LC et al. Whole genome and transcriptome sequencing of post-mortem cardiac tissues from sudden cardiac death victims identifies a gene regulatory variant in NEXN. Int J Legal Med 2019; 133: 1699–1709.
Labels
Addictology Allergology and clinical immunology Angiology Audiology Clinical biochemistry Dermatology & STDs Paediatric gastroenterology Paediatric surgery Paediatric cardiology Paediatric neurology Paediatric ENT Paediatric psychiatry Paediatric rheumatology Diabetology Pharmacy Vascular surgery Pain management Dental HygienistArticle was published in
Journal of Czech Physicians
Most read in this issue
- Hippocratic Oath and current medical oaths
- Management of Graves’ ophthalmopathy – 2022 update
- 125 let od narození profesora Josefa Charváta
- The importance of molecular autopsy in forensic medicine