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Sinnvolle Diagnostik: Genetik

Meaningful diagnostics: genetics

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Zusammenfassung

Die molekulargenetische Untersuchung ist bei einigen kardiovaskulären Erkrankungen ein wichtiger Baustein der Diagnostik. Dabei hängt die diagnostische Wertigkeit der genetischen Untersuchung maßgeblich von anamnestischen und klinischen Faktoren wie dem Vorliegen einer positiven Familienanamnese und dem Krankheitsphänotyp ab. Bei kardiovaskulären Erkrankungen mit hohen Mutationsdetektionsraten wie der hypertrophen Kardiomyopathie oder primären Arrhythmiesyndromen (Long-QT-Syndrom, katecholaminerge polymorphe ventrikuläre Tachykardie) sollte die genetische Analyse zum Standard-Work-up gehören. Einen besonderen Stellenwert hat die genetische Diagnostik darüber hinaus bei der systematischen Untersuchung von Familienangehörigen der Betroffenen (Kaskadenscreening), um asymptomatische Mutationsträger rechtzeitig erkennen und präventiv therapieren zu können. Eine spezielle Indikation zur genetischen Diagnostik stellt die molekulare Autopsie, also die postmortale molekulargenetische DNA-Analyse dar. Sie dient v. a. beim plötzlichen Herztod der Todesursachenaufklärung durch den Nachweis krankheitsspezifischer Genmutationen. Bei selektivem Einsatz und sorgfältiger Interpretation der Ergebnisse können die molekulargenetischen Analysen einen sinnvollen diagnostischen und prognostischen Beitrag leisten. Perspektivisch werden sich die Anwendungsgebiete der genetischen Analysen vermutlich auch auf polygene kardiovaskuläre Krankheitsbilder ausweiten. Hier erlauben die neuen Hochdurchsatztechnologien die Bestimmung zahlreicher Varianten in unterschiedlichen Genen, die dann in polygenen Risiko-Scores zur Vorhersage der Erkrankungswahrscheinlichkeit herangezogen werden können.

Abstract

Molecular genetic analysis is an important component in the diagnostics of some cardiovascular diseases; however, genetic testing should not be used as a screening technique as the diagnostic value strongly depends on anamnestic and clinical factors, such as a positive family history and the disease phenotype. In cardiovascular diseases with high mutation detection rates, e.g. hypertrophic cardiomyopathy and primary arrhythmia syndromes (long QT syndrome, catecholaminergic polymorphic ventricular tachycardia) genetic testing should be included in the diagnostic work-up. Family screening of first-degree relatives (cascade screening) is a particularly important application of genetic diagnostics for a timely identification of asymptomatic mutation carriers and initiation of preventive treatment. A molecular autopsy, also known as postmortem molecular genetic DNA testing, is a special indication for genetic diagnostics. It is particularly useful in the analysis of sudden cardiac death victims for the identification of disease-specific gene mutations. Therefore, given a selective use and a thorough evaluation of the test results, molecular genetic analyses can make a meaningful diagnostic and prognostic contribution. Potential applications of genetic analyses in the future are polygenic cardiovascular diseases. The use of new high-throughput technologies enables the analysis of multiple genetic variants, which can then be included in the calculation of a polygenic risk score for the prediction of the probability of a specific disease.

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Authors and Affiliations

  1. Klinik für Herz- und Kreislauferkrankungen, Deutsches Herzzentrum München, Technische Universität München, Lazarettstr. 36, 80636, München, Deutschland

    Teresa Trenkwalder, Heribert Schunkert & Wibke Reinhard

  2. Partner Site Munich Heart Alliance, Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK), München, Deutschland

    Heribert Schunkert

Authors
  1. Teresa Trenkwalder
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  2. Heribert Schunkert
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Correspondence to Wibke Reinhard.

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Interessenkonflikt

T. Trenkwalder, H. Schunkert und W. Reinhard geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Trenkwalder, T., Schunkert, H. & Reinhard, W. Sinnvolle Diagnostik: Genetik. Herz 45, 3–9 (2020). https://doi.org/10.1007/s00059-019-04875-1

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