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Considering complexity in the genetic evaluation of dilated cardiomyopathy
  1. Elizabeth Jordan1,
  2. Ray E Hershberger1,2
  1. 1 Division of Human Genetics, The Ohio State University, Columbus, Ohio, USA
  2. 2 Division of Cardiovascular Medicine, The Ohio State University, Columbus, Ohio, USA
  1. Correspondence to Ms Elizabeth Jordan, Division of Human Genetics, The Ohio State University, Columbus, OH 43210, USA; Elizabeth.jordan{at}osumc.edu

Abstract

Dilated cardiomyopathy (DCM) is a cardiovascular disease of genetic aetiology that causes substantial morbidity and mortality, and presents considerable opportunity for disease mitigation and prevention in those at risk. Foundational to the process of caring for patients diagnosed with DCM is a clinical genetic evaluation, which always begins with a comprehensive family history and clinical evaluation. Genetic testing of the proband, the first patient identified in a family with DCM, within the context of genetic counselling is always indicated, regardless of whether the DCM is familial or non-familial. Clinical screening of at-risk family members is also indicated, as is cascade genetic testing for actionable variants found at genetic testing in the proband. Clinicians now have expansive panels with many genes available for DCM genetic testing, and the approaches used to evaluate rare variants to decide which are disease-causing continues to rapidly evolve. Despite these recent advances, only a minority of cases yield actionable variants, even in familial DCM where a genetic aetiology is highly likely. This underscores that our knowledge of DCM clinical genetics remains incomplete, including variant interpretation and DCM genetic architecture. Emerging data suggest that the single-variant Mendelian disease model is insufficient to explain some DCM cases, and rather that multiple variants, both common and rare, and at times key environmental factors, interact to cause DCM. A simple model illustrating the intersection of DCM genetic architecture with environmental impact is provided.

  • idiopathic dilated cardiomyopathy
  • genetics

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Footnotes

  • Contributors EJ and RH wrote the manuscript and collaboratively developed the tables and figures.

  • Funding This work is supported by the National Heart, Lung, and Blood Institute and National Human Genome Research Institute of the National Institutes of Health under award number R01 HL128857 to RH.

  • Disclaimer The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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