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. 2020 Jan;28(1):17-22.
doi: 10.1038/s41431-019-0500-8. Epub 2019 Sep 18.

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

Najim Lahrouchi  1 , Hariharan Raju  2   3 , Elisabeth M Lodder  1 , Stathis Papatheodorou  2   3 , Chris Miles  2   3 , James S Ware  4   5 , Michael Papadakis  2   3 , Rafik Tadros  1   6 , Della Cole  2   3 , Jonathan R Skinner  7   8 , Jackie Crawford  7 , Donald R Love  7 , Chee J Pua  9 , Bee Y Soh  9 , Jaydutt D Bhalshankar  9 , Risha Govind  4   5 , Jacob Tfelt-Hansen  10 , Bo G Winkel  10 , Christian van der Werf  1 , Yanushi D Wijeyeratne  2   3 , Greg Mellor  2   3 , Janice Till  3   4   5 , Marta Cohen  11 , Maria Tome-Esteban  2   3 , Sanjay Sharma  2   3 , Arthur A M Wilde  1 , Stuart A Cook  4   9   12 , Mary N Sheppard #  2   3 , Connie R Bezzina #  1 , Elijah R Behr #  13   14
Affiliations

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

Najim Lahrouchi et al. Eur J Hum Genet. 2020 Jan.

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.

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Conflict of interest statement

AAMW has undertaken consulting for Sorin in the past. ERB has received unrestricted research funds from Biotronik and St Jude Medical. The remaining authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Overview of structural finding during autopsy and yield of genetic testing. Figure summarising autopsy findings and yield of genetic testing in cases with autopsy findings diagnostic of cardiomyopathy (a, c) and cases with autopsy findings of uncertain significance (b, d). ACM arrhythmogenic cardiomyopathy, CAD coronary artery disease, DCM dilated cardiomyopathy, HCM hypertrophic cardiomyopathy, IF idiopathic fibrosis, ILVH idiopathic left ventricular hypertrophy, LP likely pathogenic, MVP mitral valve prolapse, P pathogenic
See this image and copyright information in PMC

References

    1. Finocchiaro G, Papadakis M, Robertus J-L, Dhutia H, Steriotis AK, Tome M, et al. Etiology of Sudden Death in Sports. J Am Coll Cardiol. 2016;67:2108–15. doi: 10.1016/j.jacc.2016.02.062. - DOI - PubMed
    1. Bagnall RD, Weintraub RG, Ingles J, Duflou J, Yeates L, Lam L, et al. A prospective study of sudden cardiac death among children and young adults. N Engl J Med. 2016;374:2441–52. doi: 10.1056/NEJMoa1510687. - DOI - PubMed
    1. Landry CH, Allan KS, Connelly KA, Cunningham K, Morrison LJ, Dorian P. Sudden cardiac arrest during participation in competitive sports. N Engl J Med. 2017;377:1943–53. doi: 10.1056/NEJMoa1615710. - DOI - PMC - PubMed
    1. Lahrouchi N, Behr ER, Bezzina CR. Next-generation sequencing in post-mortem genetic testing of young sudden cardiac death cases. Front Cardiovasc Med. 2016;3:13. doi: 10.3389/fcvm.2016.00013. - DOI - PMC - PubMed
    1. Lahrouchi N, Raju H, Lodder EM, Papatheodorou E, Ware JS, Papadakis M, et al. Utility of post-mortem genetic testing in cases of sudden arrhythmic death syndrome. J Am Coll Cardiol. 2017;69:2134–45. doi: 10.1016/j.jacc.2017.02.046. - DOI - PMC - PubMed

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