Cardiomyopathy

Comprehensive Cardiomyopathy Panel

  • ApolloGen’s cardiomyopathy panel detects target genes associated with inherited cardiomyopathies, including Hypertrophic Cardiomyopathy (HCM), Dilated Cardiomyopathy (DCM), Restrictive Cardiomyopathy (RCM), Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), and Left Ventricular Non-Compaction (LVNC). The causal genes for Danon Syndrome, Fabry disease, Barth Syndrome, and Transthyretin Amyloidosis are also included in this panel. Either a comprehensive Cardiomyopathy panel, a HCM, or a DCM specialized panel may be ordered.
  • Genes(44): ABCC9, ACTC1, ACTN2, BMPR2, CAV3, DES, GLA, LAMA4, LAMP2, LDB3, LMNA, MT-TD, MT-TG, MT-TH, MT-TI, MT-TK, MT-TL1, MT-TL2, MT-TM, MT-TQ, MT-TS1, MT-TS2, MYBPC3, MYH6, MYH7, MYL2, MYL3, MYPN, PLN, PRKAG2, PSEN1, PSEN2, RBM20, SCN5A, SGCD, TAZ, TCAP, TMPO, TNNC1, TNNI3, TNNT2, TPM1, TTR, and VCL
  • Turn-Around Time: 4 Weeks
  • Test Info Sheet: Comprehensive Cardiomyopathy Panel
  • Requisitions: General Test Requisition Form
  • Preferred Specimen: 6-9 mL Blood – Lavender Tube Top
  • Other Specimens: See details here
  • Pricing: Please contact us at (949)916-8886 or inquiries@apollogen.com

  • Individuals who are affected by or have a family history of cardiac diseases, cardiomyopathy, heart failure, or sudden cardiac arrest (SCA).
  • Individuals who are affected by or have a family history of syndromic disorders associated with cardiomyopathy or mitochondrial dysfunctions, including Danon Syndrome, Fabry disease, MELAS Syndrome and MERRF Syndrome.
  • Individuals who are concerned about their own genetic risks and are interested in learning about their health risk for these diseases. These individuals are encouraged to consult their healthcare professional about ordering this test.

  • Early diagnosis
  • Early prophylactic or medical intervention
  • Risk evaluation for family members

About

  • The major types of cardiomyopathy are[3]: Dilated cardiomyopathy (DCM), Hypertrophic cardiomyopathy (HCM), Restrictive cardiomyopathy (RCM), Arrhythmogenic right ventricular dysplasia (ARVD), and Other types of cardiomyopathy (unclassified).

Cardiomyopathy can be either acquired or inherited. Etiologies of cardiomyopathy include heart attacks, coronary heart disease, high blood pressure, diabetes, pregnancy, viral infections, and certain toxins or drugs. Moreover, an increasing number of genetic aberrations have been identified as causative factors of cardiomyopathy, especially in cases with family histories of cardiomyopathy[4,5] of cardiomyopathy patients. It can also evaluate the carrier status of family members and assess the chances of parents passing the disease to their children. Genetic testing also provides important information for the patients, families and their physicians to determine the most appropriate prophylactic or medical management plan, especially for the patient who is still asymptomatic.

Variant Classification

Sequencing results will be interpreted and reported following recommendations of the American College of Medical Genetics (www.acmg.net). Sequence variations will be analyzed and classified into the following categories based on current scientific knowledge. Variants found in categories 1-3 (pathogenic, likely pathogenic, and variants of unknown clinical significance) will be reported.

  1. Pathogenic: Pathogenic variants include nonsense mutations and frameshift mutations that are predicted to result in premature protein truncation, splice site mutations, previously reported missense mutations that are recognized as disease-causing by databases and scientific literatures.
  2. Likely Pathogenic: Likely pathogenic variants are those variants that likely adversely affect the gene function, but without conclusive evidence to strongly support pathogenicity.
  3. Variant of Unknown Clinical Significance (VUS): VUS are sequence variations without sufficient evidence to either confirm or exclude pathogenicity.
  4. Likely Benign: Likely benign variants are variations for which there are significant, but not conclusive, evidence supporting that the variant is not disease-causing.
  5. Negative: A negative classification is reported when no disease-causing variant is found or is classified as a benign polymorphism based on the population data, or of no clinical significance based on review of the literature, mutation database.

Testing Methodology

Genomic DNA is extracted from the patient’s specimen and fragmented via sonication. All of the exons, flanking intronic (at least 10 nucleotide into the introns), and untranslated regions (5’ and 3’) of the targeted genes are enriched using capture-based hybridization. Massively parallel sequencing is applied to the enriched target DNA regions to detect mutation. The region <10-fold coverage is regarded as low coverage region and will be rescued by Sanger Sequencing. Variants with an allele frequency > 1% are considered likely benign polymorphisms, and are not included in the final report. Interpretation of rare alterations with allele frequency <1% is based on ACMG guidelines. All pathogenic and likely pathogenic variants are verified by Sanger Sequencing.

Massive parallel sequencing can reliably detect insertion/deletion mutations smaller than 10 base pair. However, larger insertion, deletion, duplication due to rearrangement, and mutations in regulatory and deep intronic regions cannot be detected by this technology. Rare primer site variants may lead to erroneous results that may need further investigation.

References

  1. P. Richardson, W. McKenna, M. Bristow, B. Maisch, B. Mautner, J. O’Connell, et al., Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomyopathies, Circulation. 93 (1996) 841–842.
  2. A. Luk, E. Ahn, G.S. Soor, J. Butany, Dilated cardiomyopathy: a review, J. Clin. Pathol. 62 (2009) 219–225. doi:10.1136/jcp.2008.060731.
  3. P. Elliott, B. Andersson, E. Arbustini, Z. Bilinska, F. Cecchi, P. Charron, et al., Classification of the cardiomyopathies: a position statement from the european society of cardiology working group on myocardial and pericardial diseases, Eur Heart J. 29 (2008) 270–276. doi:10.1093/eurheartj/ehm342.
  4. M.J. Puckelwartz, E.M. McNally, Genetic profiling for risk reduction in human cardiovascular disease, Genes (Basel). 5 (2014) 214–234. doi:10.3390/genes5010214.
  5. J.G. Seidman, C. Seidman, The genetic basis for cardiomyopathy: from mutation identification to mechanistic paradigms, Cell. 104 (2001) 557–567.

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