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Long QT syndrome mutation detection by SNaPshot technique

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Abstract

Long QT syndrome (LQTS) is a cardiac disorder with an abnormality of cardiac rhythm associated with sudden death especially in younger, apparently healthy individuals. If there is no clear cause of death detectable during comprehensive coroner's inquest (autopsy-negative cases), you have to consider LQTS and other heritable arrhythmia syndromes. A molecular genetic screening regarding mutations in associated genes can help to ensure the cause of death and to protect affected family members. Genetic testing of LQTS, currently performed mainly by sequencing, is still very expensive and time consuming. With this study we present a rapid and reasonable method for the simultaneously screening of some of the most common mutations associated with LQTS, focused on the KCNQ1 and KCNH2 genes. With the method of SNaPshot minisequencing, a total of 58 mutations were analyzed in four multiplex assays which were successfully established and optimized. The comparison with samples previously analyzed by direct sequencing showed concordance. Furthermore, autopsy-negative cases were tested but no mutations could be observed in any of the specimen. The presented method is well suitable for LQTS mutation screening. An enhancement to further mutations and population-based investigations regarding mutation frequencies should be the aim of prospective studies.

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Acknowledgments

The authors would like to thank Ms. Manuela Pigors for her studies and support.

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Authors and Affiliations

  1. Institute of Forensic Medicine, University of Leipzig, Leipzig, Germany

    Jeanett Edelmann & Marina Nastainczyk

  2. Institute of Forensic Medicine, University of Münster, Münster, Germany

    Stefanie Schumann

  3. Department of Internal Medicine/Cardiology, Heart Center University Leipzig, Leipzig, Germany

    Daniela Husser-Bollmann

  4. Institute of Forensic Medicine, University of Halle, Halle, Germany

    Rüdiger Lessig

Authors
  1. Jeanett Edelmann
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  2. Stefanie Schumann
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  3. Marina Nastainczyk
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  4. Daniela Husser-Bollmann
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  5. Rüdiger Lessig
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Corresponding author

Correspondence to Jeanett Edelmann.

Electronic supplementary material

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Table S1a

Primer sequences of KCNQ1 exon multiplex PCR (DOC 31 kb)

Table S1b

Primer sequences of KCNH2 exon multiplex PCR (DOC 31 kb)

Table S2a

KCNQ1—SNP primer sequences of the first primer combination (DOC 44 kb)

Table S2b

KCNQ1—SNP primer sequences of the second primer combination (DOC 44 kb)

Table S3a

KCNH2—SNP primer sequences of the third primer combination (DOC 43 kb)

Table S3b

KCNH2—SNP primer sequences of the fourth primer combination (DOC 41 kb)

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Edelmann, J., Schumann, S., Nastainczyk, M. et al. Long QT syndrome mutation detection by SNaPshot technique. Int J Legal Med 126, 969–973 (2012). https://doi.org/10.1007/s00414-011-0598-x

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  • DOI: https://doi.org/10.1007/s00414-011-0598-x

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