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The yield of postmortem genetic testing in sudden death cases with structural findings at autopsy.

Lahrouchi, N; Raju, H; Lodder, EM; Papatheodorou, S; Miles, C; Ware, JS; Papadakis, M; Tadros, R; Cole, D; Skinner, JR; et al. Lahrouchi, N; Raju, H; Lodder, EM; Papatheodorou, S; Miles, C; Ware, JS; Papadakis, M; Tadros, R; Cole, D; Skinner, JR; Crawford, J; Love, DR; Pua, CJ; Soh, BY; Bhalshankar, JD; Govind, R; Tfelt-Hansen, J; Winkel, BG; van der Werf, C; Wijeyeratne, YD; Mellor, G; Till, J; Cohen, M; Tome-Esteban, M; Sharma, S; Wilde, AAM; Cook, SA; Sheppard, MN; Bezzina, CR; Behr, ER (2020) The yield of postmortem genetic testing in sudden death cases with structural findings at autopsy. Eur J Hum Genet, 28 (1). pp. 17-22. ISSN 1476-5438 https://doi.org/10.1038/s41431-019-0500-8
SGUL Authors: Behr, Elijah Raphael Sheppard, Mary Noelle Tome, Maria Teresa Miles, Christopher Jason

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Abstract

Sudden cardiac death (SCD) is often associated with structural abnormalities of the heart during autopsy. This study sought to compare the diagnostic yield of postmortem genetic testing in (1) cases with structural findings of uncertain significance at autopsy to (2) cases with autopsy findings diagnostic of cardiomyopathy. We evaluated 57 SCD cases with structural findings at cardiac autopsy. Next-generation sequencing using a panel of 77 primary electrical disorder and cardiomyopathy genes was performed. Pathogenic and likely pathogenic variants were classified using American College of Medical Genetics (ACMG) consensus guidelines. In 29 cases (51%) autopsy findings of uncertain significance were identified whereas in 28 cases (49%) a diagnosis of cardiomyopathy was established. We identified a pathogenic or likely pathogenic variant in 10 cases (18%); in 1 (3%) case with non-specific autopsy findings compared with 9 (32%) cases with autopsy findings diagnostic of cardiomyopathy (p = 0.0054). The yield of genetic testing in SCD cases with autopsy findings consistent with cardiomyopathy is comparable with the yield in cardiomyopathy patients that are alive. Genetic testing in cases with findings of uncertain significance offers lower clinical utility than in cardiomyopathy, with lower yields than detected previously. This highlights the need for stringent evaluation of variant pathogenicity.

Item Type: Article
Additional Information: This is a post-peer-review, pre-copyedit version of an article published in European Journal of Human Genetics. The final authenticated version is available online at: http://dx.doi.org/10.1038/s41431-019-0500-8
Keywords: 0604 Genetics, Genetics & Heredity
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: Eur J Hum Genet
ISSN: 1476-5438
Language: eng
Dates:
DateEvent
January 2020Published
18 September 2019Published Online
12 August 2019Accepted
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
FS/11/71/28918British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
PubMed ID: 31534214
Go to PubMed abstract
URI: http://openaccess.sgul.ac.uk/id/eprint/111234
Publisher's version: https://doi.org/10.1038/s41431-019-0500-8

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