Evidence-Based Assessment of Genes in Dilated Cardiomyopathy

作者：Elizabeth Jordan, Laiken Peterson, Tomohiko Ai, Babken Asatryan, Lucas Bronicki, Emily E. Brown, Rudy Celeghin, Matthew M. Edwards, Judy Fan, Jodie Ingles, Cynthia A. James, Olga Jarinova, Renée Johnson, Daniel Philip Judge, Najim Lahrouchi, Ronald H. Lekanne Deprez, R Thomas Lumbers, Francesco Mazzarotto, Argelia Medeiros‐Domingo, Rebecca L. Miller, Ana Morales, Brittney A. Murray, Stacey A. Peters, Kalliopi Pilichou, Alexandros Protonotarios, Christopher Semsarian, Palak Mayur Shah, Petros Syrris, Courtney Thaxton, J. Peter van Tintelen, Roddy Walsh, Jessica Wang, James S. Ware, Ray E. Hershberger · 发表于：Circulation · 年份：2021 · DOI：10.1161/circulationaha.120.053033 · 被引用次数：538 · 研究领域：Cardiovascular Effects of Exercise、Cardiomyopathy and Myosin Studies、Eosinophilic Disorders and Syndromes

BACKGROUND: Each of the cardiomyopathies, classically categorized as hypertrophic cardiomyopathy, dilated cardiomyopathy (DCM), and arrhythmogenic right ventricular cardiomyopathy, has a signature genetic theme. Hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are largely understood as genetic diseases of sarcomere or desmosome proteins, respectively. In contrast, >250 genes spanning >10 gene ontologies have been implicated in DCM, representing a complex and diverse genetic architecture. To clarify this, a systematic curation of evidence to establish the relationship of genes with DCM was conducted. METHODS: An international panel with clinical and scientific expertise in DCM genetics evaluated evidence supporting monogenic relationships of genes with idiopathic DCM. The panel used the Clinical Genome Resource semiquantitative gene-disease clinical validity classification framework with modifications for DCM genetics to classify genes into categories on the basis of the strength of currently available evidence. Representation of DCM genes on clinically available genetic testing panels was evaluated. RESULTS: ) including 2 additional ontologies were classified as moderate evidence; these genes are likely to emerge as strong or definitive with additional evidence. Of these 19 genes, 6 were similarly classified for hypertrophic cardiomyopathy and 3 for arrhythmogenic right ventricular cardiomyopathy. Of the remaining 32 genes (63%), 25 (49%) had li...