Post-mortem genetic testing in sudden cardiac death and genetic screening of relatives at risk: lessons learned from a Czech pilot multidisciplinary study
Jazyk angličtina Země Německo Médium print-electronic
Typ dokumentu časopisecké články
Grantová podpora
NV18-02-00237
Ministry of Health, Czech Republic
NV15-27682A
Ministry of Health, Czech Republic
CZ.2.16/3.1.00/24022
European Regional Development Fund
NF-CZ11-PDP-3-003-2014
Norway Grants
PubMed
37178278
PubMed Central
PMC10567875
DOI
10.1007/s00414-023-03007-z
PII: 10.1007/s00414-023-03007-z
Knihovny.cz E-zdroje
- Klíčová slova
- Forensic genetics, Inherited cardiovascular diseases, Molecular autopsy, Sudden cardiovascular death, Sudden death prevention,
- MeSH
- dospělí MeSH
- genetické testování * MeSH
- lidé středního věku MeSH
- lidé MeSH
- náhlá srdeční smrt * etiologie MeSH
- pilotní projekty MeSH
- pitva * MeSH
- studie proveditelnosti MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
Sudden cardiac death (SCD) might have an inherited cardiac condition background. Genetic testing supports post-mortem diagnosis and screening of relatives at risk. Our aim is to determine the feasibility of a Czech national collaboration group and to establish the clinical importance of molecular autopsy and family screening. From 2016 to 2021, we have evaluated 100 unrelated SCD cases (71.0% males, age: 33.3 (12.8) years). Genetic testing was performed by next-generation sequencing utilizing a panel of 100 genes related to inherited cardiac/aortic conditions and/or whole exome sequencing. According to autopsy, cases were divided into cardiomyopathies, sudden arrhythmic death syndrome, sudden unexplained death syndrome, and sudden aortic death. We identified pathogenic/likely pathogenic variants following ACMG/AMP recommendations in 22/100 (22.0%) of cases. Since poor DNA quality, we have performed indirect DNA testing in affected relatives or in healthy parents reaching a diagnostic genetic yield of 11/24 (45.8%) and 1/10 (10.0%), respectively. Cardiological and genetic screening disclose 83/301 (27.6%) relatives at risk of SCD. Genetic testing in affected relatives as starting material leads to a high diagnostic yield offering a valuable alternative when suitable material is not available. This is the first multidisciplinary/multicenter molecular autopsy study in the Czech Republic which supports the establishment of this type of diagnostic tests. A central coordinator and proper communication among centers are crucial for the success of a collaboration at a national level.
Department of Biology and Medical Genetics University Hospital Ostrava Ostrava Czech Republic
Department of Forensic Medicine and Toxicology Liberec Regional Hospital Liberec Czech Republic
Department of Medical Genetics University Hospital Pilsen Pilsen Czech Republic
Forensic Department Hospital České Budějovice České Budějovice Czech Republic
Forensic Department of Military University Hospital Prague Czech Republic
Institute for Forensic Medicine 3rd Faculty of Medicine Charles University Prague Czech Republic
Paediatric Department 3rd Faculty of Medicine Charles University Prague Czech Republic
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