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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

The yield of postmortem genetic testing in sudden death cases with structural findings at autopsy. / Lahrouchi, Najim; Raju, Hariharan; Lodder, Elisabeth M; Papatheodorou, Stathis; Miles, Chris; Ware, James S; Papadakis, Michael; Tadros, Rafik; Cole, Della; Skinner, Jonathan R; Crawford, Jackie; Love, Donald R; Pua, Chee J; Soh, Bee Y; Bhalshankar, Jaydutt D; Govind, Risha; Tfelt-Hansen, Jacob; Winkel, Bo G; van der Werf, Christian; Wijeyeratne, Yanushi D; Mellor, Greg; Till, Janice; Cohen, Marta; Tome-Esteban, Maria; Sharma, Sanjay; Wilde, Arthur A M; Cook, Stuart A; Sheppard, Mary N; Bezzina, Connie R; Behr, Elijah R.

In: European Journal of Human Genetics, Vol. 18, 2020, p. 17-22.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

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', European Journal of Human Genetics, vol. 18, pp. 17-22. https://doi.org/10.1038/s41431-019-0500-8

APA

Lahrouchi, N., Raju, H., Lodder, E. M., Papatheodorou, S., Miles, C., Ware, J. S., Papadakis, M., Tadros, R., Cole, D., Skinner, J. R., Crawford, J., Love, D. R., Pua, C. J., Soh, B. Y., Bhalshankar, J. D., Govind, R., Tfelt-Hansen, J., Winkel, B. G., van der Werf, C., ... Behr, E. R. (2020). The yield of postmortem genetic testing in sudden death cases with structural findings at autopsy. European Journal of Human Genetics, 18, 17-22. https://doi.org/10.1038/s41431-019-0500-8

Vancouver

Lahrouchi N, Raju H, Lodder EM, Papatheodorou S, Miles C, Ware JS et al. The yield of postmortem genetic testing in sudden death cases with structural findings at autopsy. European Journal of Human Genetics. 2020;18:17-22. https://doi.org/10.1038/s41431-019-0500-8

Author

Lahrouchi, Najim ; Raju, Hariharan ; Lodder, Elisabeth M ; Papatheodorou, Stathis ; Miles, Chris ; Ware, James S ; Papadakis, Michael ; Tadros, Rafik ; Cole, Della ; Skinner, Jonathan R ; Crawford, Jackie ; Love, Donald R ; Pua, Chee J ; Soh, Bee Y ; Bhalshankar, Jaydutt D ; Govind, Risha ; Tfelt-Hansen, Jacob ; Winkel, Bo G ; van der Werf, Christian ; Wijeyeratne, Yanushi D ; Mellor, Greg ; Till, Janice ; Cohen, Marta ; Tome-Esteban, Maria ; Sharma, Sanjay ; Wilde, Arthur A M ; Cook, Stuart A ; Sheppard, Mary N ; Bezzina, Connie R ; Behr, Elijah R. / The yield of postmortem genetic testing in sudden death cases with structural findings at autopsy. In: European Journal of Human Genetics. 2020 ; Vol. 18. pp. 17-22.

Bibtex

@article{60d236a40fa140f5af90ef78f0d017f1,
title = "The yield of postmortem genetic testing in sudden death cases with structural findings at autopsy",
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.",
author = "Najim Lahrouchi and Hariharan Raju and Lodder, {Elisabeth M} and Stathis Papatheodorou and Chris Miles and Ware, {James S} and Michael Papadakis and Rafik Tadros and Della Cole and Skinner, {Jonathan R} and Jackie Crawford and Love, {Donald R} and Pua, {Chee J} and Soh, {Bee Y} and Bhalshankar, {Jaydutt D} and Risha Govind and Jacob Tfelt-Hansen and Winkel, {Bo G} and {van der Werf}, Christian and Wijeyeratne, {Yanushi D} and Greg Mellor and Janice Till and Marta Cohen and Maria Tome-Esteban and Sanjay Sharma and Wilde, {Arthur A M} and Cook, {Stuart A} and Sheppard, {Mary N} and Bezzina, {Connie R} and Behr, {Elijah R}",
year = "2020",
doi = "10.1038/s41431-019-0500-8",
language = "English",
volume = "18",
pages = "17--22",
journal = "European Journal of Human Genetics",
issn = "1018-4813",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - The yield of postmortem genetic testing in sudden death cases with structural findings at autopsy

AU - Lahrouchi, Najim

AU - Raju, Hariharan

AU - Lodder, Elisabeth M

AU - Papatheodorou, Stathis

AU - Miles, Chris

AU - Ware, James S

AU - Papadakis, Michael

AU - Tadros, Rafik

AU - Cole, Della

AU - Skinner, Jonathan R

AU - Crawford, Jackie

AU - Love, Donald R

AU - Pua, Chee J

AU - Soh, Bee Y

AU - Bhalshankar, Jaydutt D

AU - Govind, Risha

AU - Tfelt-Hansen, Jacob

AU - Winkel, Bo G

AU - van der Werf, Christian

AU - Wijeyeratne, Yanushi D

AU - Mellor, Greg

AU - Till, Janice

AU - Cohen, Marta

AU - Tome-Esteban, Maria

AU - Sharma, Sanjay

AU - Wilde, Arthur A M

AU - Cook, Stuart A

AU - Sheppard, Mary N

AU - Bezzina, Connie R

AU - Behr, Elijah R

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

U2 - 10.1038/s41431-019-0500-8

DO - 10.1038/s41431-019-0500-8

M3 - Journal article

C2 - 31534214

VL - 18

SP - 17

EP - 22

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

SN - 1018-4813

ER -

ID: 227822781