Modern molecular genetic methods in forensic diagnosis of sudden cardiac death: a review

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Abstract

Sudden cardiac death remains one of the leading causes of premature mortality among the working-age population, particularly in young individuals. In a substantial proportion of cases, conventional autopsy methods fail to establish a definitive cause of death. The need for new diagnostic approaches to unexplained deaths has led to the emergence and rapid development of the concept of molecular autopsy. This review analyzes the applications, limitations, and prospects of molecular genetic methods in forensic practice. This review discusses current knowledge on the genetic basis of inherited arrhythmias and cardiomyopathies, the leading causes of sudden death in the absence of structural myocardial abnormalities. The evolution of technologies is outlined, from Sanger sequencing, which formed the basis of early molecular autopsies, to next-generation sequencing, which now enables the simultaneous analysis of hundreds of genes associated with arrhythmogenic disorders. Particular attention is given to the interpretation of genetic variants, classification of their clinical significance, challenges in analyzing variants of uncertain significance, and the need for their reclassification as scientific evidence accumulates. A separate section addresses cascade family testing as a key element in preventing recurrent cases of sudden death and in organizing genetic counseling for relatives. The review substantiates the rationale for integrating molecular autopsy into the forensic medical system as a tool to enhance the evidentiary value of conclusions and to promote interdisciplinary integration of forensic medicine, cardiology, and clinical genetics. The analysis demonstrates that molecular autopsy not only expands diagnostic capabilities but also provides a foundation for the development of preventive medicine aimed at reducing inherited sudden deaths.

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About the authors

Yana V. Fomina

Kuban State Medical University

Author for correspondence.
Email: fominyana2000@gmail.com
ORCID iD: 0000-0001-9453-4086
SPIN-code: 4422-4692
Russian Federation, 14 Mitrofana Lavrentyeva st, Krasnodar, 350063

Rasul Ya. Akmurzaev

North Ossetian State Medical Academy

Email: akmurzaevrasul@mail.ru
ORCID iD: 0009-0008-8833-107X
Russian Federation, Vladikavkaz

Anna I. Gagloeva

North Ossetian State Medical Academy

Email: Annagagloeva12@gmail.com
ORCID iD: 0009-0008-5718-9605
Russian Federation, Vladikavkaz

Arina A. Dzugutova

North Ossetian State Medical Academy

Email: dzugutovaari@mail.ru
ORCID iD: 0009-0002-2772-1679
Russian Federation, Vladikavkaz

Aishat O. Dzhamaldinova

North Ossetian State Medical Academy

Email: aisha0330@mail.ru
ORCID iD: 0009-0007-7255-7405
Russian Federation, Vladikavkaz

Lidiya V. Kuleshova

Kuban State Medical University

Email: lkuleshova76@gmail.com
ORCID iD: 0009-0000-0593-226X
Russian Federation, 14 Mitrofana Lavrentyeva st, Krasnodar, 350063

Sabina A. Amirkhanova

Volgograd State Medical University

Email: amirhanova.sabina@gmail.com
ORCID iD: 0009-0007-9218-1185
Russian Federation, Volgograd

Ekaterina D. Shlyakova

Volgograd State Medical University

Email: shlyakova-2002@mail.ru
ORCID iD: 0009-0008-9356-7968
Russian Federation, Volgograd

Polina A. Barba

Ryazan State Medical University named after Academician I.P. Pavlov

Email: Polina_tmb_2002@mail.ru
ORCID iD: 0009-0003-0845-3637
Russian Federation, Ryazan

Polina S. Ishkova

The Russian National Research Medical University named after N.I. Pirogov (Pirogov University)

Email: ishkova.polina2002@gmail.com
ORCID iD: 0009-0008-7950-1399
Russian Federation, Moscow

Anastasia A. Mitina

The Russian National Research Medical University named after N.I. Pirogov (Pirogov University)

Email: anastasi.m1tina@yandex.ru
ORCID iD: 0009-0000-2541-0143
Russian Federation, Moscow

Amalia R. Vovchenko

The Russian National Research Medical University named after N.I. Pirogov (Pirogov University)

Email: iamalia189@gmail.com
ORCID iD: 0009-0005-6924-2985
Russian Federation, Moscow

Anastasiya A. Novikova

The Russian National Research Medical University named after N.I. Pirogov (Pirogov University)

Email: Noviknate@yandex.ru
ORCID iD: 0009-0008-7494-043X
Russian Federation, Moscow

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СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
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