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Genetic screening in sudden cardiac death in the young can save future lives

Stattin, Eva-Lena; Westin, Ida Maria; Cederquist, Kristina; Jonasson, Jenni; Jonsson, Bjoern-Anders; Moerner, Stellan; Norberg, Anna; Krantz, Peter LU and Wisten, Aase (2016) In International Journal of Legal Medicine 130(1). p.59-66
Abstract
Autopsy of sudden cardiac death (SCD) in the young shows a structurally and histologically normal heart in about one third of cases. Sudden death in these cases is believed to be attributed in a high percentage to inherited arrhythmogenic diseases. The purpose of this study was to investigate the value of performing post-mortem genetic analysis for autopsy-negative sudden unexplained death (SUD) in 1 to 35 year olds. From January 2009 to December 2011, samples from 15 cases suffering SUD were referred to the Department of Clinical Genetics, UmeAyen University Hospital, Sweden, for molecular genetic evaluation. PCR and bidirectional Sanger sequencing of genes important for long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome... (More)
Autopsy of sudden cardiac death (SCD) in the young shows a structurally and histologically normal heart in about one third of cases. Sudden death in these cases is believed to be attributed in a high percentage to inherited arrhythmogenic diseases. The purpose of this study was to investigate the value of performing post-mortem genetic analysis for autopsy-negative sudden unexplained death (SUD) in 1 to 35 year olds. From January 2009 to December 2011, samples from 15 cases suffering SUD were referred to the Department of Clinical Genetics, UmeAyen University Hospital, Sweden, for molecular genetic evaluation. PCR and bidirectional Sanger sequencing of genes important for long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome type 1 (BrS1), and catecholaminergic polymorphic ventricular tachycardia (CPVT) (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, and RYR2) was performed. Multiplex ligation-dependent probe amplification (MLPA) was used to detect large deletions or duplications in the LQTS genes. Six pathogenic sequence variants (four LQTS and two CPVT) were discovered in 15 SUD cases (40 %). Ten first-degree family members were found to be mutation carriers (seven LQTS and three CPVT). Cardiac ion channel genetic testing in autopsy-negative sudden death victims has a high diagnostic yield, with identification of the disease in 40 % of families. First-degree family members should be offered predictive testing, clinical evaluation, and treatment with the ultimate goal to prevent sudden death. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Sudden unexplained death, Sudden cardiac death, Molecular autopsy, Long, QT syndrome, Catecholaminergic polymorphic ventricular tachycardia
in
International Journal of Legal Medicine
volume
130
issue
1
pages
59 - 66
publisher
Springer
external identifiers
  • wos:000368685400006
  • scopus:84954360690
ISSN
0937-9827
DOI
10.1007/s00414-015-1237-8
language
English
LU publication?
yes
id
70fae96a-fd35-4648-b1be-903bec56509c (old id 8731622)
date added to LUP
2016-03-01 07:15:31
date last changed
2017-10-01 04:14:40
@article{70fae96a-fd35-4648-b1be-903bec56509c,
  abstract     = {Autopsy of sudden cardiac death (SCD) in the young shows a structurally and histologically normal heart in about one third of cases. Sudden death in these cases is believed to be attributed in a high percentage to inherited arrhythmogenic diseases. The purpose of this study was to investigate the value of performing post-mortem genetic analysis for autopsy-negative sudden unexplained death (SUD) in 1 to 35 year olds. From January 2009 to December 2011, samples from 15 cases suffering SUD were referred to the Department of Clinical Genetics, UmeAyen University Hospital, Sweden, for molecular genetic evaluation. PCR and bidirectional Sanger sequencing of genes important for long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome type 1 (BrS1), and catecholaminergic polymorphic ventricular tachycardia (CPVT) (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, and RYR2) was performed. Multiplex ligation-dependent probe amplification (MLPA) was used to detect large deletions or duplications in the LQTS genes. Six pathogenic sequence variants (four LQTS and two CPVT) were discovered in 15 SUD cases (40 %). Ten first-degree family members were found to be mutation carriers (seven LQTS and three CPVT). Cardiac ion channel genetic testing in autopsy-negative sudden death victims has a high diagnostic yield, with identification of the disease in 40 % of families. First-degree family members should be offered predictive testing, clinical evaluation, and treatment with the ultimate goal to prevent sudden death.},
  author       = {Stattin, Eva-Lena and Westin, Ida Maria and Cederquist, Kristina and Jonasson, Jenni and Jonsson, Bjoern-Anders and Moerner, Stellan and Norberg, Anna and Krantz, Peter and Wisten, Aase},
  issn         = {0937-9827},
  keyword      = {Sudden unexplained death,Sudden cardiac death,Molecular autopsy,Long,QT syndrome,Catecholaminergic polymorphic ventricular tachycardia},
  language     = {eng},
  number       = {1},
  pages        = {59--66},
  publisher    = {Springer},
  series       = {International Journal of Legal Medicine},
  title        = {Genetic screening in sudden cardiac death in the young can save future lives},
  url          = {http://dx.doi.org/10.1007/s00414-015-1237-8},
  volume       = {130},
  year         = {2016},
}