Author + information
- Received July 29, 2019
- Revision received September 25, 2019
- Accepted October 10, 2019
- Published online December 2, 2019.
- Diane Fatkin, MDa,b,c,∗ (, )@FatkinLab,
- Inken G. Huttner, MDa,b,
- Jason C. Kovacic, MD, PhDd,
- J.G. Seidman, PhDe,f and
- Christine E. Seidman, MDf,g
- aMolecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia
- bSt. Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, Kensington, New South Wales, Australia
- cCardiology Department, St. Vincent’s Hospital, Darlinghurst, New South Wales, Australia
- dThe Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York
- eHoward Hughes Medical Institute, Boston, Massachusetts
- fDepartment of Genetics, Harvard Medical School, Boston, Massachusetts
- gCardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Diane Fatkin, Victor Chang Cardiac Research Institute, 405 Liverpool Street, Darlinghurst, New South Wales 2010, Australia.
• Human genome sequencing is now readily available and affordable, but data interpretation and knowing how to use genetic information in individual patient management remains challenging.
• Genomic-based precision medicine in DCM requires more widespread use and a higher yield of genetic testing, as well as an understanding of the functional effects of genetic variants and their prognostic significance.
• The use of genetics for future DCM prevention will rely on accurate detection of individuals at risk, and evidence-based data for the optimal timing and type of therapeutic intervention.
Precision medicine promises to dramatically improve patient outcomes and reduce health care costs through a shift in focus from disease treatment to prevention and individualized therapies. For families with inherited cardiomyopathies, efforts to date have been directed toward discovery and functional characterization of single disease-causing variants. With advances in sequencing, the cataloging of personal genetic variation has been expedited, providing improved insights into the key importance of the genes in which variants occur. These advances have propelled seminal opportunities for successful variant-targeted disease-reversing therapy. New challenges have also emerged—particularly interpretation of the rapidly rising numbers of “variants of unknown significance.” For treatments based on patient genotype to be feasible on a wider scale, these obstacles need to be overcome. Here the authors focus on genetics of dilated cardiomyopathy and provide a roadmap for implementing genomic information into future patient management.
This work was supported by the National Health and Medical Research Council, Estate of the Late R.T. Hall, Simon Lee Foundation, and St. Vincent’s Clinic Foundation. Drs. Fatkin and Huttner have received support from Victor Chang Cardiac Research Institute. Dr. Kovacic has received honoraria from Medtronic. Drs. Kovacic and J.G. Seidman have received support from the National Institutes of Health. Prof. J.G. Seidman and Dr. C.E. Seidman have received support from the Leducq Foundation; and are founders of and own shares in Myokardia Inc., a startup company that is developing therapeutics that target the sarcomere, which had no involvement in this study. Dr. C.E. Seidman has received support from Howard Hughes Medical Institute.
- Received July 29, 2019.
- Revision received September 25, 2019.
- Accepted October 10, 2019.
- 2019 American College of Cardiology Foundation
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