Journal of Clinical Medicine Article Mitochondrial DNA: Hotspot for Potential Gene Modifiers Regulating Hypertrophic Cardiomyopathy Parisa K. Kargaran 1, Jared M. Evans 2, Sara E. Bodbin 3, James G. W. Smith 4 , Timothy J. Nelson 5, Chris Denning 3,* and Diogo Mosqueira 3,* 1 Department of Cardiovascular Medicine, Center for Regenerative Medicine, Mayo Clinic, Rochester, MN 55905, USA;
[email protected] 2 Department of Health Science Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN 55905, USA;
[email protected] 3 Division of Cancer and Stem Cells, Biodiscovery Institute, University of Nottingham, Nottingham NG7 2RD, UK;
[email protected] 4 Faculty of Medicine and Health Sciences, Norwich Medical School, University of East Anglia, Norwich NR4 7UQ, UK;
[email protected] 5 Division of General Internal Medicine, Division of Pediatric Cardiology, Departments of Medicine, Molecular Pharmacology, and Experimental Therapeutics, Mayo Clinic Center for Regenerative Medicine, Rochester, MN 55905, USA;
[email protected] * Correspondence:
[email protected] (C.D.);
[email protected] (D.M.) Received: 22 June 2020; Accepted: 21 July 2020; Published: 23 July 2020 Abstract: Hypertrophic cardiomyopathy (HCM) is a prevalent and untreatable cardiovascular disease with a highly complex clinical and genetic causation. HCM patients bearing similar sarcomeric mutations display variable clinical outcomes, implying the involvement of gene modifiers that regulate disease progression. As individuals exhibiting mutations in mitochondrial DNA (mtDNA) present cardiac phenotypes, the mitochondrial genome is a promising candidate to harbor gene modifiers of HCM. Herein, we sequenced the mtDNA of isogenic pluripotent stem cell-cardiomyocyte models of HCM focusing on two sarcomeric mutations.