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07.12.2018 | Commentary

Genetic testing in sudden unexpected natural death in the young: New York City Office of Chief Medical Examiner’s experience and perspective

verfasst von: Yingying Tang, Nori Williams, Barbara A. Sampson

Erschienen in: Forensic Science, Medicine and Pathology | Ausgabe 3/2019

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Abstract

Postmortem genetic testing is a diagnostic tool that is becoming increasingly utilized. The benefits and limitations of genetic testing in cases of sudden, unexpected death in the young (≤ 40 years old) are reviewed from the perspective of the Office of Chief Medical Examiner of the City of New York, whose Molecular Genetics Laboratory, accredited by College of American Pathologists, has had 15 years of postmortem testing experience. Challenges to the interpretation and communication of testing results are highlighted, and opportunities for improving testing yield are discussed for age groups across the lifespan, from infancy to adulthood.
Literatur
1.
Zurück zum Zitat Wang D, Shah KR, Um SY, et al. Cardiac channelopathy testing in 274 ethnically diverse sudden unexplained deaths. Forensic Sci Int. 2014;237:90–9.CrossRefPubMed Wang D, Shah KR, Um SY, et al. Cardiac channelopathy testing in 274 ethnically diverse sudden unexplained deaths. Forensic Sci Int. 2014;237:90–9.CrossRefPubMed
4.
Zurück zum Zitat Haynes RL, Frelinger AL 3rd, Giles EK, et al. High serum serotonin in sudden infant death syndrome. Proc Natl Acad Sci U S A. 2017;114:7695–700.CrossRefPubMedPubMedCentral Haynes RL, Frelinger AL 3rd, Giles EK, et al. High serum serotonin in sudden infant death syndrome. Proc Natl Acad Sci U S A. 2017;114:7695–700.CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Sadeh D, Shannon DC, Abboud S, Saul JP, Akselrod S, Cohen RJ. Altered cardiac repolarization in some victims of sudden infant death syndrome. N Engl J Med. 1987;317:1501–5.CrossRefPubMed Sadeh D, Shannon DC, Abboud S, Saul JP, Akselrod S, Cohen RJ. Altered cardiac repolarization in some victims of sudden infant death syndrome. N Engl J Med. 1987;317:1501–5.CrossRefPubMed
6.
Zurück zum Zitat Perticone F, Ceravolo R, Maio R, Cosco C, Mattioli PL. Heart rate variability and sudden infant death syndrome. Pacing Clin Electrophysiol. 1990;13:2096–9.CrossRefPubMed Perticone F, Ceravolo R, Maio R, Cosco C, Mattioli PL. Heart rate variability and sudden infant death syndrome. Pacing Clin Electrophysiol. 1990;13:2096–9.CrossRefPubMed
7.
Zurück zum Zitat Schwartz PJ, Stramba-Badiale M, Segantini A, et al. Prolongation of the QT interval and the sudden infant death syndrome. N Engl J Med. 1998;338:1709–14.CrossRefPubMed Schwartz PJ, Stramba-Badiale M, Segantini A, et al. Prolongation of the QT interval and the sudden infant death syndrome. N Engl J Med. 1998;338:1709–14.CrossRefPubMed
8.
Zurück zum Zitat Neyroud N, Tesson F, Denjoy I, et al. A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome. Nat Genet. 1997;15:186–9.CrossRefPubMed Neyroud N, Tesson F, Denjoy I, et al. A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome. Nat Genet. 1997;15:186–9.CrossRefPubMed
9.
Zurück zum Zitat Gando I, Morganstein J, Jana K, McDonald TV, Tang Y, Coetzee WA. Infant sudden death: Mutations responsible for impaired Nav1.5 channel trafficking and function. Pacing Clin Electrophysiol. 2017;40:703–12.CrossRefPubMed Gando I, Morganstein J, Jana K, McDonald TV, Tang Y, Coetzee WA. Infant sudden death: Mutations responsible for impaired Nav1.5 channel trafficking and function. Pacing Clin Electrophysiol. 2017;40:703–12.CrossRefPubMed
10.
Zurück zum Zitat Tester DJ, Wong LCH, Chanana P, et al. Exome-wide rare variant analyses in sudden infant death syndrome. J Pediatr. 2018;203:423–8 e11.CrossRefPubMed Tester DJ, Wong LCH, Chanana P, et al. Exome-wide rare variant analyses in sudden infant death syndrome. J Pediatr. 2018;203:423–8 e11.CrossRefPubMed
11.
Zurück zum Zitat Mates J, Mademont-Soler I, Del Olmo B, et al. Role of copy number variants in sudden cardiac death and related diseases: genetic analysis and translation into clinical practice. Eur J Hum Genet. 2018;26:1014–25.CrossRefPubMedPubMedCentral Mates J, Mademont-Soler I, Del Olmo B, et al. Role of copy number variants in sudden cardiac death and related diseases: genetic analysis and translation into clinical practice. Eur J Hum Genet. 2018;26:1014–25.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Yoshinaga M, Kucho Y, Ushinohama H, Ishikawa Y, Ohno S, Ogata H. Autonomic function and QT interval during night-time sleep in infant long QT syndrome. Circ J. 2018;82:2152–9.CrossRefPubMed Yoshinaga M, Kucho Y, Ushinohama H, Ishikawa Y, Ohno S, Ogata H. Autonomic function and QT interval during night-time sleep in infant long QT syndrome. Circ J. 2018;82:2152–9.CrossRefPubMed
13.
Zurück zum Zitat Weintraub RG, Gow RM, Wilkinson JL. The congenital long QT syndromes in childhood. J Am Coll Cardiol. 1990;16:674–80.CrossRefPubMed Weintraub RG, Gow RM, Wilkinson JL. The congenital long QT syndromes in childhood. J Am Coll Cardiol. 1990;16:674–80.CrossRefPubMed
14.
Zurück zum Zitat Georgievskaya Z, Tang Y, Williams N, Sampson B, Gelb BD, Kontorovich AR. Fatal myocarditis is associated with rare cardiomyopathy gene variants. Circulation. 2018;136:A18206. Georgievskaya Z, Tang Y, Williams N, Sampson B, Gelb BD, Kontorovich AR. Fatal myocarditis is associated with rare cardiomyopathy gene variants. Circulation. 2018;136:A18206.
15.
Zurück zum Zitat Tang Y, Sampson B, Pack S, et al. Ethnic differences in out-of-hospital fatal pulmonary embolism. Circulation. 2011;123:2219–25.CrossRefPubMed Tang Y, Sampson B, Pack S, et al. Ethnic differences in out-of-hospital fatal pulmonary embolism. Circulation. 2011;123:2219–25.CrossRefPubMed
16.
Zurück zum Zitat Halvorsen M, Lin Y, Sampson BA, et al. Whole exome sequencing reveals severe thrombophilia in acute unprovoked idiopathic fatal pulmonary embolism. EBioMedicine. 2017;17:95–100.CrossRefPubMedPubMedCentral Halvorsen M, Lin Y, Sampson BA, et al. Whole exome sequencing reveals severe thrombophilia in acute unprovoked idiopathic fatal pulmonary embolism. EBioMedicine. 2017;17:95–100.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Gago-Diaz M, Ramos-Luis E, Zoppis S, et al. Postmortem genetic testing should be recommended in sudden cardiac death cases due to thoracic aortic dissection. Int J Legal Med. 2017;131:1211–9.CrossRefPubMed Gago-Diaz M, Ramos-Luis E, Zoppis S, et al. Postmortem genetic testing should be recommended in sudden cardiac death cases due to thoracic aortic dissection. Int J Legal Med. 2017;131:1211–9.CrossRefPubMed
18.
Zurück zum Zitat Chen J, Weber M, Um SY, Walsh CA, Tang Y, McDonald TV. A dual mechanism for I (Ks) current reduction by the pathogenic mutation KCNQ1-S277L. Pacing Clin Electrophysiol. 2011;34:1652–64.CrossRefPubMedPubMedCentral Chen J, Weber M, Um SY, Walsh CA, Tang Y, McDonald TV. A dual mechanism for I (Ks) current reduction by the pathogenic mutation KCNQ1-S277L. Pacing Clin Electrophysiol. 2011;34:1652–64.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Gerull B, Heuser A, Wichter T, et al. Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy. Nat Genet. 2004;36:1162–4.CrossRefPubMed Gerull B, Heuser A, Wichter T, et al. Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy. Nat Genet. 2004;36:1162–4.CrossRefPubMed
20.
Zurück zum Zitat Williams N, Marion R, McDonald TV, et al. Phenotypic variations in carriers of predicted protein-truncating genetic variants in MYBPC3: an autopsy-based case series. Cardiovasc Pathol. 2018;37:30–3.CrossRefPubMed Williams N, Marion R, McDonald TV, et al. Phenotypic variations in carriers of predicted protein-truncating genetic variants in MYBPC3: an autopsy-based case series. Cardiovasc Pathol. 2018;37:30–3.CrossRefPubMed
21.
Zurück zum Zitat Sampson BA, Tang Y. Holistic approach to determine cause of autopsy-negative sudden natural death. J Am Coll Cardiol. 2017;69:2146–8.CrossRefPubMed Sampson BA, Tang Y. Holistic approach to determine cause of autopsy-negative sudden natural death. J Am Coll Cardiol. 2017;69:2146–8.CrossRefPubMed
Metadaten
Titel
Genetic testing in sudden unexpected natural death in the young: New York City Office of Chief Medical Examiner’s experience and perspective
verfasst von
Yingying Tang
Nori Williams
Barbara A. Sampson
Publikationsdatum
07.12.2018
Verlag
Springer US
Erschienen in
Forensic Science, Medicine and Pathology / Ausgabe 3/2019
Print ISSN: 1547-769X
Elektronische ISSN: 1556-2891
DOI
https://doi.org/10.1007/s12024-018-0068-6

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