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International Journal of Legal Medicine

, Volume 132, Issue 4, pp 1057–1065 | Cite as

Exome analysis in 34 sudden unexplained death (SUD) victims mainly identified variants in channelopathy-associated genes

  • Jacqueline Neubauer
  • Maria Rita Lecca
  • Giancarlo Russo
  • Christine Bartsch
  • Argelia Medeiros-Domingo
  • Wolfgang Berger
  • Cordula Haas
Original Article

Abstract

Sudden cardiac death (SCD) is one of the major causes of mortality worldwide, mostly involving coronary artery disease in the elderly. In contrary, sudden death events in young victims often represent the first manifestation of undetected genetic cardiac diseases, which remained without any symptoms during lifetime. Approximately 30% of these sudden death cases have no definite cardiac etiology after a comprehensive medicolegal investigation and are therefore termed as sudden unexplained death (SUD) cases. Advances in high-throughput sequencing approaches have provided an efficient diagnostic tool to identify likely pathogenic variants in cardiovascular disease-associated genes in otherwise autopsy-negative SUD cases. The aim of this study was to genetically investigate a cohort of 34 unexplained death cases by focusing on candidate genes associated with cardiomyopathies and channelopathies. Exome analysis identified potentially disease-causing sequence alterations in 29.4% of the 34 SUD cases. Six (17.6%) individuals had variants with likely functional effects in the channelopathy-associated genes AKAP9, KCNE5, RYR2, and SEMA3A. Interestingly, four of these six SUD individuals were younger than 18 years of age. Since the total SUD cohort of this study included five children and adolescents, post-mortem molecular autopsy screening indicates a high diagnostic yield within this age group. Molecular genetic testing represents a valuable approach to uncover the cause of death in some of the SUD victims; however, 70–80% of the cases still remain elusive, emphasizing the importance of additional research to better understand the pathological mechanisms leading to a sudden death event.

Keywords

Sudden unexplained death Molecular autopsy Whole-exome sequencing Cardiovascular diseases Channelopathies 

Notes

Acknowledgments

This project was supported by the Swiss National Science Foundation (SNF; project-Nr. 320030_149456). Special thanks to Corinne Moser for DNA extractions and Sanger sequencing.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Supplementary material

414_2018_1775_MOESM1_ESM.pdf (230 kb)
ESM 1 (PDF 230 kb).

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Jacqueline Neubauer
    • 1
  • Maria Rita Lecca
    • 2
  • Giancarlo Russo
    • 2
  • Christine Bartsch
    • 3
  • Argelia Medeiros-Domingo
    • 4
  • Wolfgang Berger
    • 5
    • 6
    • 7
  • Cordula Haas
    • 1
  1. 1.Zurich Institute of Forensic Medicine, Forensic GeneticsUniversity of ZurichZurichSwitzerland
  2. 2.Functional Genomics Center Zurich (FGCZ)University of Zurich/ETH ZurichZurichSwitzerland
  3. 3.University of ZurichZurichSwitzerland
  4. 4.Department of Cardiology, InselspitalUniversity Hospital BernBernSwitzerland
  5. 5.Institute of Medical Molecular GeneticsUniversity of ZurichSchlierenSwitzerland
  6. 6.Center for Integrative Human Physiology (ZIHP)University of ZurichZurichSwitzerland
  7. 7.Neuroscience Center (ZNZ)University of Zurich/ETH ZurichZurichSwitzerland

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