Affiliation:
1. Research Institute of Therapy and Preventive Medicine, Federal Research Center Institute of Cytology and Genetics; Novosibirsk State Medical University
2. Research Institute of Therapy and Preventive Medicine, Federal Research Center Institute of Cytology and Genetics
3. Novosibirsk State Medical University
4. Novosibirsk Regional Clinical Bureau of Forensic Medicine
5. Novosibirsk State Medical University; Novosibirsk Regional Clinical Bureau of Forensic Medicine
Abstract
Aim.To search for causal mutations in candidate genes responsible for the development of sudden cardiac death (SCD) in men who died under the age of 45.Materialandmethods.The SCD group (n=37) was formed using the criteria the World Health Organization and the European Society of Cardiology. Autopsy material was collected from men who died suddenly outside medical institutions and underwent forensic medical examination according to the standard protocol. Autopsy revealed no morphological changes that could explain sudden death. The mean age was 32,4±6,4 years. Genomic DNA was isolated from myocardial tissue using phenol-chloroform extraction. Clinical exome sequencing was performed. At first, we analyzed the results of sequencing of 24 genes, mutations in which lead to cardiovascular diseases associated with an increased risk of SCD:KCNQ1,KCNH2,SCN5A,AKAP9,ANK2,CACNA1C,CALM1,CALM2,CAV3,KCNE1,KNCJNE2,KCNE2,SCN4B,SNTA1,MYH2,APOB,KCNA5,TGFB3,NEB,PDX1,FLNC,PLEC,KCND3.Results.Of 37 samples, we revealed 13 probable pathogenic missense mutations in 9 samples (24,3%). Of 13 probable pathogenic variants, 5 were new.Conclusion.This pilot study provides following conclusions: it is necessary to continue molecular autopsy research in Russia; to increase the effectiveness of detecting causal mutations, it is necessary to reduce the age of patients with SCD included in the study; studying the families of deceased; cooperation of experienced specialists — forensic pathologist, laboratory geneticist, cardiologist.
Subject
Cardiology and Cardiovascular Medicine
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