Myopathic Cardiac Genotypes Increase Risk for Myocarditis

Amy R Kontorovich; Nihir Patel; Arden Moscati; Felix Richter; Inga Peter; Enkhsaikhan Purevjav; Simina Ramona Selejan; Ingrid Kindermann; Jeffrey A Towbin; Michael Bohm; Karin Klingel; Bruce D Gelb

doi:10.1016/j.jacbts.2021.06.001

Myopathic Cardiac Genotypes Increase Risk for Myocarditis

JACC Basic Transl Sci. 2021 Jul 26;6(7):584-592. doi: 10.1016/j.jacbts.2021.06.001. eCollection 2021 Jul.

Authors

Amy R Kontorovich^{1

2}, Nihir Patel^{2

3}, Arden Moscati⁴, Felix Richter², Inga Peter³, Enkhsaikhan Purevjav⁵, Simina Ramona Selejan⁶, Ingrid Kindermann⁶, Jeffrey A Towbin⁵, Michael Bohm⁶, Karin Klingel⁷, Bruce D Gelb^{2

3

8}

Affiliations

¹ Zena and Michael A. Weiner Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
² The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
³ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁴ The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁵ Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
⁶ Department of Internal Medicine III (Cardiology, Angiology and Intensive Care), Saarland University Medical Center, Saarland University, Homburg/Saar, Germany.
⁷ Cardiopathology, Institute for Pathology and Neuropathology, University Hospital Tuebingen, Tuebingen, Germany.
⁸ Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Abstract

Impairments in certain cardiac genes confer risk for myocarditis in children. To determine the extent of this association, we performed genomic sequencing in predominantly adult patients with acute myocarditis and matched control subjects. Putatively deleterious variants in a broad set of cardiac genes were found in 19 of 117 acute myocarditis cases vs 34 of 468 control subjects (P = 0.003). Thirteen genes classically associated with cardiomyopathy or neuromuscular disorders with cardiac involvement were implicated, including >1 associated damaging variant in DYSF, DSP, and TTN. Phenotypes of subjects who have acute myocarditis with or without deleterious variants were similar, indicating that genetic testing is necessary to differentiate them.

Keywords: ACM, arrhythmogenic cardiomyopathy; AM, acute myocarditis; AM1, acute myocarditis registry 1; CMP, cardiomyopathy; DV, deleterious variant; EF, ejection fraction; ES, exome sequencing; NMD, neuromuscular disorder; OR, odds ratio; TGP, targeted gene panel; acute myocarditis; cardiomyopathy; genetics.

Abstract

Grants and funding