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Myopathic Cardiac Genotypes Increase Risk for Myocarditis
- Source :
- JACC: Basic to Translational Science
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Visual Abstract<br />Highlights • AM is an important cause of cardiac dysfunction following some viral infections and has been previously linked with genetic host susceptibilities. • Sequencing data for genes related to cardiomyocyte structure and function was compared between patients with AM and sex- and ancestry-matched heart-healthy control subjects. • Putatively DVs among these genes were found in ∼16% of AM cases, contributing to viral susceptibility. • Implicated genes are ones classically associated with cardiomyopathy or neuromuscular disorders with cardiac involvement, suggesting shared mechanistic pathways. • Phenotypes, including outcomes, were similar in subjects who have AM with and without DV, therefore genetic testing will be necessary to uncover this subtype and inform risk in relatives.<br />Summary 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.
- Subjects :
- Myocarditis
ACM, arrhythmogenic cardiomyopathy
Cardiomyopathy
Disease
Bioinformatics
acute myocarditis
DV, deleterious variant
Clinical Research
AM1, acute myocarditis registry 1
Genotype
medicine
EF, ejection fraction
genetics
TGP, targeted gene panel
Gene
Exome sequencing
Genetic testing
medicine.diagnostic_test
business.industry
ES, exome sequencing
Myocardial Disorder
medicine.disease
Control subjects
Phenotype
CMP, cardiomyopathy
OR, odds ratio
Acute myocarditis
AM, acute myocarditis
Heart failure
Immunology
Cardiology and Cardiovascular Medicine
business
cardiomyopathy
NMD, neuromuscular disorder
Subjects
Details
- ISSN :
- 2452302X
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- JACC: Basic to Translational Science
- Accession number :
- edsair.doi.dedup.....7a4650779dee78b43bbea0b4c9341047