Genetic testing is defined as the analysis of chromosomes, deoxyribonucleic acid, or ribonucleic acid to identify genetic variants that may be of medical significance. Most genetic tests involve direct detection of a mutation responsible for disease or risk of disease. Linkage-based tests rely on use of genetic markers that reside nearby a gene of interest to track inheritance of the gene in a family. This approach is used less often as the genes involved in disease risk are increasingly amenable to direct testing. A third approach, referred to as genomic testing, involves analysis of multiple genetic variants or products of gene expression to obtain an overall “genomic fingerprint” of an individual or tissue sample.
Coronary artery disease is the leading cause of death in the world, affecting 13,000,000 people in the U.S. alone. As such, it is a major public health concern, and significant efforts have sought to reduce the mortality and morbidity associated with CAD. These efforts have focused primarily on modification of environmental and behavioral risk factors, including sedentary lifestyle, smoking, obesity, and high-fat diet. Modifying these behaviors is extremely important, and has been shown to reduce cardiovascular mortality and morbidity. Nonetheless, family history remains the single strongest independent risk factor for development of CAD. However, in most cases this risk cannot be determined more precisely. The information gained through a detailed family history does not identify specific interventions to limit risk, nor can it assist in determining a treatment plan. Thus, identification of specific genetic risk factors is essential for more precise risk determination, as well as individualization of therapy. Testing for such factors will be beneficial not only for those with a positive family history, but also could benefit healthy individuals with no family history. Although such uses of genetic tests are not currently available, the pace of discovery promises clinically useful tests in the near future.
| Disorder | Inheritance Pattern | Gene Product |
|---|---|---|
| DCM | ||
| Pure familial DCM | AD | actin |
| AD | desmin | |
| AD | γ-sarcoglycan | |
| AD | tropinin T | |
| AD | β-myosin heavy chain⁎ | |
| AD | CSRP3 | |
| AD | phospholamban | |
| (1 case) | TCAP | |
| DCM with ventricular tachycardia | (2 cases) | ABCC9 |
| DCM with wooly hair and keratoderma | AR | desmoplakin |
| DCM plus cardiac conduction defects (Emery-Dreifuss muscular dystrophy) | AD | lamin A/C⁎ |
| X-linked DCM (Duchene/Becker muscular dystrophy) | XLR | dystrophin⁎ |
| X-linked DCM (also Barth syndrome, isolated noncompaction of the ventricular myocardium) | XLR | tafazzin⁎ |
| Isolated noncompaction of the ventricular myocardium | AD | α-dystrobrevin |
| AD | Cypher/ZASP | |
| AD | lamin A/C⁎ | |
| HCM (192600) | ||
| HCM | AD | α-tropomyosin⁎ |
| AD | cardiac myosin-binding protein C⁎ | |
| AD | β-myosin heavy chain⁎ | |
| AD | tropinin T | |
| AD | myosin light chain | |
| AD | cardiac troponin I | |
| AD | myosin light chain 3 | |
| AD | titan | |
| AD | myosin heavy chain-α | |
| Mito | tRNA-glycine | |
| Mito | tRNA-isoleucine | |
| HCM and DCM | ||
| Primarily causes HCM; only 1 patient with DCM | AD | cardiac myosin-binding protein |
| AD | β-myosin heavy chain | |
| AD | actin | |
| AD | cardiac myosin light-peptide kinase | |
| AD | caveolin-3 | |
| AD | α-tropomyosin | |
| Arrythmogenic right ventricular dysplasia | ||
| AD | ryanodine receptor | |
| AD | desmoplakin | |
| AD | plakophilin 2 |
AD =autosomal dominant; AR = autosomal recessive; DCM = dilated cardiomyopathy; HCM = hypertrophic cardiomyopathy; Mito = mitochondrial; XLR = X-linked recessive.
Cardiomyopathy is typically divided into several subtypes: dilated, hypertrophic, arrhythmogenic right ventricular dysplasia, restrictive, and unclassified.
