Download Arrhythmogenic Cardiomyopathy Panel Up to 23 genes

Test Information Sheet
Arrhythmogenic Cardiomyopathy Panel
Up to 23 genes
The Arrhythmogenic Cardiomyopathy Panel is a comprehensive next-generation sequencing (NGS) panel
that includes genes related to cardiomyopathy conditions with prominent arrhythmias. This test can be used
to confirm a clinical diagnosis or identify at-risk individuals.
Disorders of the heart can include abnormalities of the heart muscle (cardiomyopathies), irregularities of the
heart’s electrical system leading to irregular heartbeats (arrhythmias), or both. One condition that features
cardiomyopathy with prominent arrhythmia is arrhythmogenic right ventricular cardiomyopathy (dysplasia).
Arrhythmogenic right ventricular cardiomyopathy is characterized by the progressive replacement of normal
heart muscle with fibrous fatty tissue. This predisposes individuals to irregular heart rhythms, including
ventricular tachycardia, and sudden death in some cases.
PREVALENCE
The prevalence of arrhythmogenic right ventricular cardiomyopathy is estimated to be 1 in 1,000 to 1 in 1,250
individuals (Peters, 2006).
INCLUDED DISORDERS
This panel includes genes associated with:
•
Arrhythmogenic right ventricular cardiomyopathy
(dysplasia)
•
Hypertrophic cardiomyopathy and arrhythmias
•
Dilated cardiomyopathy and arrhythmias
•
Other conditions that include both cardiomyopathy
and arrhythmias as features
CLINICAL SENSITIVITY
Disease causing mutations can be identified in
approximately 50% of arrhythmogenic right ventricular
cardiomyopathy cases (Quarta et al, 2011). The
Arrhythmogenic Right Ventricular Cardiomyopathy Panel
includes all of the genes commonly associated with this
disease.
methods. Copy number variants, including intragenic
deletions and duplications are detected to a resolution of
single exon. To request analysis of a specific single exon
copy number variant, please contact our Client Services
team prior to ordering. Analytical sensitivity of the assay
is >99%.
INHERITANCE AND PENETRANCE
Arrhythmogenic right ventricular cardiomyopathy (ARVC)
is typically inherited in autosomal dominant manner,
although Emery-Dreifuss muscular dystrophy, caused by
mutations in the EMD gene, is inherited in an X-linked
manner, and Naxos disease, caused by mutations in the
JUP gene, is inherited in an autosomal recessive manner.
Compound heterozygosity and digenic inheritance has
also been reported (Bauce et al, 2010; Xu et al, 2010).
Arrhythmogenic right ventricular cardiomyopathy exhibits
reduced penetrance. In one family with a mutation in
the DSP gene, the penetrance was 50% (Rampazzo et
al, 2002), and in other families with dominant ARVC, the
penetrance was estimated at 20-30% (Chowdhury et al,
2005).
METHODOLOGY AND ANALYTICAL SENSITIVITY
Next-generation sequencing technology is used to
test clinically relevant portions of each gene, including
coding exons, adjacent intron/exon boundaries, and
selected introns/noncoding variants. Pathogenic and
likely pathogenic variants are confirmed by orthogonal
© Phosphorus 2017
www. phosphorus.com | 1-855-746-7423 | [email protected]
032017 ACTIS 1.0
INDICATIONS FOR TESTING
•
Confirmation of a clinical diagnosis
•
Unexplained cardiac arrest
•
Cardiomyopathy and arrhythmia
•
Risk assessment for asymptomatic family of members of proband with molecular diagnosis of arrhythmogenic right
ventricular cardiomyopathy or other arrhythmogenic cardiomyopathy
INCLUDED GENES (20):
ACTN2
DES
DSC2
DSG2
DSP
EMD
JUP
LDB3
LMNA
PKP2
PLN
PRKAG2
RBM20
RYR2
SCN5A
TGFB3
TMEM43
TNNI3
TNNT2
TTN
ADDITIONS TO THE COMPREHENSIVE PANEL
Emerging Evidence Genes (3):
Emerging evidence genes can also be added on to the Arrhythmogenic Cardiomyopathy panel. These genes do not
have a clear association with arrhythmogenic cardiomyopathy, but emerging evidence suggests that they may play a
role in disease pathogenicity.
ANKRD1
CTNNA3
PDLIM3
REFERENCES
1. Bauce B, Nava A, Beffagna G, et al. Multiple mutations in desmosomal proteins encoding genes in arrhythmogenic right ventricular
cardiomyopathy/dysplasia. Heart Rhythm. 2010;7(1):22-9.
2. Peters S. Advances in the diagnostic management of arrhythmogenic right ventricular dysplasia-cardiomyopathy. Int J Cardiol. 2006;113(1):4-11.
3. Quarta G, Muir A, Pantazis A, et al. Familial evaluation in arrhythmogenic right ventricular cardiomyopathy: impact of genetics and revised task
force criteria. Circulation. 2011;123(23):2701-9.
4. Rampazzo A, Nava A, Malacrida S, et al. Mutation in human desmoplakin domain binding to plakoglobin causes a dominant form of arrhythmogenic
right ventricular cardiomyopathy. Am J Hum Genet. 2002;71(5):1200-6.
5. Sen-chowdhry S, Syrris P, Mckenna WJ. Genetics of right ventricular cardiomyopathy. J Cardiovasc Electrophysiol. 2005;16(8):927-35.
6. Xu T, Yang Z, Vatta M, et al. Compound and digenic heterozygosity contributes to arrhythmogenic right ventricular cardiomyopathy. J Am Coll
Cardiol. 2010;55(6):587-97.
© Phosphorus 2017
www. phosphorus.com | 1-855-746-7423 | [email protected]
032017 ACTIS 1.0