Molecular autopsy in sudden unexplained death

Öz

Molecular autopsy is the process of investigating sudden unexplained deaths through genetic analysis. It is particularly useful in cases where the cause of death is unexplained or shows non-diagnostic features despite macroscopic, histopathological, and toxicological examinations at conventional autopsy. Postmortem genetic testing is a complementary tool to a rigorous autopsy. The ultimate purpose of molecular autopsy is to assist forensic investigations and guide the genetic screening of relatives of the victim who may be at risk for sudden unexplained death. Earlier molecular autopsy attempts relied on Sanger sequencing, which although accurate and easy to use, has a low yield and can only be used to analyze a small panel of genes. The recent adoption of next-generation sequencing (NGS) technologies has allowed for exome/genome-wide examination, resulting in an increase in detection of pathogenic variants and the discovery of newer genotype-phenotype associations. This review summarizes the scientific evidence for the use of molecular autopsy to investigate sudden unexplained deaths. Unlike other recently published articles dealing with this topic, we aimed to the technical aspects of data processing and interpretation as well as report the latest data, focusing on the use of NGS technologies for molecular autopsy.

Anahtar Kelimeler

• Autopsy
• sudden death
• molecular genetic

Ani açıklanamayan ölümlerde moleküler otopsi

Öz

Moleküler otopsi, ani açıklanamayan ölümlerin genetik analiz yoluyla araştırılması işlemidir. Geleneksel otopside makroskobik, histopatolojik, toksikolojik incelemelere karşın ölüm nedeninin açıklanamadığı veya tanısal olmayan özellikler gösterdiği durumlarda özellikle yararlıdır. Postmortem genetik testler titizlikle yapılan bir otopsi için tamamlayıcı bir araçtır. Moleküler otopsinin nihai amacı, adli tıp araştırmalarına yardımcı olmak ve mağdurun ani açıklanamayan ölümlere karşı risk altında olabilecek akrabalarının genetik taramasına rehberlik etmektir. Eski moleküler otopsi girişimleri, doğru ve kullanımı kolay olmasına rağmen, düşük bir verime sahip olan ve yalnızca küçük bir gen panelini analiz etmek için kullanılabilen Sanger dizilimine dayanıyordu. Yeni nesil dizileme (NGS) teknolojilerinin yakın zamanda benimsenmesi, ekzom/genom çapında incelemeye izin vererek, patojenik varyantların tespitinde bir artış ve daha yeni genotip-fenotip birlikteliklerinin keşfini sağlamıştır. Bu derlemede, ani açıklanamayan ölümlerin araştırması için moleküler otopsi kullanımına ilişkin bilimsel kanıtlar özetlenmekte ayrıca bu konuyu ele alan yakın zamanda yayınlanan diğer makalelerden farklı olarak moleküler otopsi için NGS teknolojilerinin kullanımına odaklanarak en son verileri, hem de veri işleme ve yorumlamaya ilişkin teknik yönleri raporlamayı amaçladık.

Anahtar Kelimeler

• Otopsi
• ani ölüm
• moleküler genetik

Kaynakça

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