Diagnostic Yield of Genetic Testing in Sudden Cardiac Death with Autopsy Findings of Uncertain Significance.

Autor:	Iglesias M; Cardiology Department, Son Llatzer University Hospital, IdISBa, CIBEROBN, 07198 Palma de Mallorca, Spain., Ripoll-Vera T; Cardiology Department, Son Llatzer University Hospital, IdISBa, CIBEROBN, 07198 Palma de Mallorca, Spain., Perez-Luengo C; Balearic Institute of Legal Medicine, 07003 Palma de Mallorca, Spain., García AB; Balearic Institute of Legal Medicine, 07003 Palma de Mallorca, Spain., Moyano S; Histopathology Department, National Institute of Toxicology and Forensic Science, 08002 Barcelona, Spain., Canos JC; Histopathology Department, National Institute of Toxicology and Forensic Science, 08002 Barcelona, Spain., Borondo JC; Histopathology Department, National Institute of Toxicology and Forensic Science, 08002 Barcelona, Spain., Alvarez J; Cardiology Department, Son Llatzer University Hospital, IdISBa, CIBEROBN, 07198 Palma de Mallorca, Spain., Heine-Suñer D; Department of Molecular Diagnosis and Clinical Genetics, Son Espases University Hospital, IdISBa, 07120 Palma de Mallorca, Spain., Barcelo B; Department of Clinical Analysis and Toxicology, Son Espases University Hospital, IdISBa, 07120 Palma de Mallorca, Spain.
Jazyk:	angličtina
Zdroj:	Journal of clinical medicine [J Clin Med] 2021 Apr 21; Vol. 10 (9). Date of Electronic Publication: 2021 Apr 21.
DOI:	10.3390/jcm10091806
Abstrakt:	Background: Sudden death (SD) in the young usually has an underlying genetic cause. In many cases, autopsy reveals unspecific and inconclusive results, like idiopathic left ventricular hypertrophy (LVH), nonsignificant coronary atherosclerosis (CA), and primary myocardial fibrosis (PMF). Their pathogenicity and their relation to SD cause is unknown. This study aims to evaluate the diagnostic yield of genetic testing in these cases. Methods: SD cases, between 1 and 50 years old, with findings of uncertain significance (idiopathic LVH, nonsignificant CA and PMF) on autopsy were evaluated prospectively, including information about medical and family history and circumstances of death. Genetic testing was performed. Results: In a series of 195 SD cases, we selected 31 cases presenting idiopathic LVH ( n = 16, 51.61%), nonsignificant CA ( n = 17, 54.84%), and/or PMF ( n = 24, 77.42%) in the autopsy. Mean age was 41 ± 7.2 years. Diagnostic yield of genetic test was 67.74%, considering variants of unknown significance (VUS), pathogenic variants (PV) and likely pathogenic variants (LPV); 6.45% including only PV and LPV. Structural genes represented 41,93% ( n = 13) of cases, while 38,7% ( n = 12) were related to channelopathies. Conclusion: Molecular autopsy in SD cases between 1 and 50 years old, with findings of uncertain significance, has a low diagnostic yield, being VUS the most frequent variant observed.
Databáze:	MEDLINE
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