Genetic Testing Program for Arrhythmogenic Right Ventricular Cardiomyopath (ARVC)

ARVC is a heart disease primarily affecting the right ventricle. It is characterized by myocardial atrophy, fibrofatty replacement of the ventricular myocardium, and inflammatory infiltrates. With disease progression and frequent left ventricle involvement (32-88%), heart failure may result. The most common symptoms include ventricular arrhythmias, recurrent syncope, seizures, and sudden death after physical or emotional stress (Marcus et al. 2010. PubMed ID: 20172911). ARVC is present in ~20% of young sudden cardiac death victims (Corrado et al. 1998. PubMed ID: 9691102). ARVC affects between 1/2,000 and 1/5,000 people worldwide with a higher prevalence in men compared to women, and typically presents in the 2nd-4th decade of life (Peters. 2006. PubMed ID: 16737750; Corrado and Thiene. 2006. PubMed ID: 16585401). For more information, see McNally et al. 2014 (PubMed ID: 20301310).

ARVC is a heterogeneous disease that is inherited in roughly 50% of the cases (Basso et al. 2004. PubMed D: 15039134). The mode of inheritance is most often autosomal dominant (AD) with age- and gender-dependent penetrance. Pathogenic variants in three genes encoding desmosomal proteins (PKP2, DSP, and DSG2) account for the great majority of known genetic causes of ARVC (McNally et al. 2014. PubMed ID: 20301310). Pathogenic variants in the DSC2 gene account for ~2% of patients with a clinical diagnosis of ARVC (Bhuiyan et al. 2009. PubMed ID: 20031616). The remaining genes are rare causes (<1-2% each) of ARVC. This panel includes 16 genes associated with ARVC: CDH2, CTNNA3, DES, DSC2, DSG2, DSP, FLNC, JUP, LDB3, LMNA, PKP2, PLN, RYR2, SCN5A, TGFB3, and TMEM43. A wide variety of causative variants (missense, nonsense, splicing, and small deletions or insertions) have been reported. Large deletions/duplications and complex genomic rearrangements have also been reported in the DES, DSP, and PKP2 genes (Human Gene Mutation Database). See individual gene test descriptions for information on molecular biology of gene products.

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 99.0% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

1. Patient is between the age of 18 - 65 years at the time of enrollment.
2. Patient has a diagnosis, or suspected diagnosis, of ARVC.

1. Determine if the individual meets eligibility criteria and discuss the test. One no-charge pre-test genetic counseling appointment with a third-party service (provided by Genome Medical) is available to patients through this sponsored testing program.
2. Order the test using the test requisition form.
3. Collect a blood, saliva, or buccal specimen in the collection tube. For information on ordering specimen kits, see Specimen Collection and Shipping section.
4. The genetic test will be processed at PreventionGenetics and the results will be sent to the ordering healthcare provider about 18 days after the lab receives the specimens and all appropriately completed paperwork.
5. The ordering healthcare provider will discuss the results with the patient and/or caregiver. One no-charge post-test genetic counseling appointment with a third-party service (provided by Genome Medical) is available to patients through this sponsored testing program.

SPECIMEN REQUIREMENTS

Whole Blood

Collect 3 ml - 5 ml of whole blood in EDTA (purple top tube) or ACD (yellow top tube), minimum 1 ml for small infants. Specimens may be refrigerated and/or shipped at room temperature.

Saliva

Oragene™ or GeneFiX™ Saliva Collection kit used according to manufacturer instructions. DNA from saliva specimens is invariably contaminated with microbial and food DNA, which can impact specimen quality and may result in delayed testing and/or the need for a second specimen. Specimens may be shipped at room temperature.

OCD-100 Buccal Swab (Preferred)

OCD-100 Buccal Swab used according to manufacturer instructions. Specimens may be shipped at room temperature.

SHIPPING AND HANDLING INSTRUCTIONS

Label all specimen containers with the patient's name, date of birth, and/or ID number. At least two identifiers should be listed on specimen containers. Specimen deliveries are accepted Monday-Saturday for all specimen types. Holiday schedules will be posted on our website at least one week prior to major holidays.