Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Dilated Cardiomyopathy (DCM) DCMNext is a multi-gene panel for patients with inherited DCM. Mutations in TTN have been found in about 20% of those with non-ischemic or idiopathic DCM, with mutations in 31 additional genes accounting for at least another 10-20%.1 Often, DCM can be asymptomatic and sudden death is the first symptom. Clinical features can be mild or uncertain; genetic testing may be the most effective way of identifying at-risk individuals or confirming a diagnosis. 2 test summary DCMNext is a next generation sequencing (NGS) and deletion/duplication panel of 32 genes associated with inherited DCM (exceptions may be specified). These genes are included in the comprehensive cardiomyopathy (CMNext) and cardiovascular genetics (CardioNext) panels. disease information DCM occurs in at least 1 in 2,700 individuals worldwide. DCM is characterized by left ventricular enlargement, with normal wall thickness and systolic dysfunction.1 Approximately half of DCM is caused by ischemic heart disease, which is typically not genetic. Mutations have been found in up to 35% of patients with non-ischemic DCM.1 Non-ischemic DCM is usually inherited in an autosomal dominant manner, but may also be autosomal recessive or X-linked. Non-ischemic DCM may present at any stage of life, but onset usually occurs in the fourth to sixth decade.1 Management for DCM typically includes echocardiograms, electrocardiograms, and assessment of sudden cardiac death risk. Medical treatment to reduce hemodynamic stress is common. Implantable cardioverter defibrillator (ICD) or pacemaker placement may be recommended if arrhythmias are not well controlled, if a patient is at high risk of sudden cardiac death, or if a particular gene is implicated by genetic testing results (e.g. LMNA). 3 DCM may present in childhood; treatment can be considered in children and adults with a high risk for DCM. Heart transplantation may be necessary for patients that develop end-stage heart failure. 2 heart rhythm society and european heart rhythm association 2011 expert consensus statement2 DCM genetic testing is a Class I recommendation for all patients with DCM and significant cardiac conduction disease and/or a family history of premature sudden death • Once a pathogenic gene mutation is identified in a family, mutation-specific testing of family members is a Class I recommendation • mutation detection rate DCMNext will find a mutation in 30-40% of patients with non-ischemic DCM, which represents all known genetic causes (clinical sensitivity). DCMNext will find >96% of described mutations in the above genes (analytic sensitivity). benefits of genetic testing Clarify diagnosis and risk for sudden cardiac arrest • Target medical management and prevention of cardiac arrest and other complications • Adjust management in those with DCM due to conditions like Duchenne muscular dystrophy and Danon disease • Offer family members genetic testing (for a familial mutation) and implement medical surveillance to only those that need it • Reduce healthcare costs, resources, and anxiety for families • OPTIMIZED TEST DESIGN Ambry’s tests are created to maximize yield, minimize turnaround time, and control costs through step-wise testing when appropriate. INSURANCE Ambry is contracted with the majority of health plans and Medicare. All outof-network patients are treated as innetwork to minimize out-of-pocket costs. Medicaid coverage varies by state and preverification is recommended. PATIENT PROTECTION PLAN If your patient’s out-of-pocket financial responsibility is potentially greater than $100, Ambry will contact him/her for verbal approval prior to initiating the test. We remain committed to working with you and your patients to make the genetic testing process as simple and cost effective as possible. CLINICAL SUPPORT Board-certified physicians and genetic counselors are available to assist with test selection and result interpretation. CUSTOMER SERVICE Responsive, knowledgeable representatives are always ready to answer your questions. We also offer easy-to-read result reports and complimentary sample submission kits to make the testing process smoother. ABOUT AMBRY GENETICS Since 2001, we have performed hundreds of thousands of genetic tests, and identified more than 45,000 mutations in greater than 500 different genes. Dilated Cardiomyopathy (DCM) test description specimen requirements DCMNext includes 32 genes associated with DCM. These genes are also included in the comprehensive cardiomyopathy (CMNext) and cardiovascular genetics panel (CardioNext). Genomic deoxyribonucleic acid (gDNA) is isolated from the patient’s specimen using a standardized kit and quantified. Sequence enrichment of the targeted coding exons and adjacent intronic nucleotides is carried out by a bait-capture methodology using long biotinylated oligonucleotide probes followed by polymerase chain reaction (PCR) and NGS. Additional Sanger sequencing is performed for any regions missing or with insufficient read depth coverage for reliable heterozygous variant detection. Suspect variant calls other than “likely benign” or “benign” are verified by Sanger sequencing in sense and antisense directions. This assay targets all coding domains and well into the flanking 5’ and 3’ ends of all the introns and untranslated regions. Gross deletion/duplication analysis for available genes is performed utilizing a targeted chromosomal microarray (for all genes except TBX1 and TXNRD2). Blood: Collect 6-10cc (adult) or at least 5cc (children) in purple top EDTA tube (preferred) or yellow top citric acetate tube. Storage: 2-8°C and do not freeze. Shipment: Room temperature for twoday delivery. Blood Spot: Blood spots are not accepted. Saliva: Fill 2 tubes with saliva up to black line (1cc of saliva) in Oragene Self Collection container. Close tube; 1cc of buffer will mix with saliva for a total volume of 2cc. Store at room temperature in sterile bag. Shipment: Room temperature for twoday delivery. DNA: 20 µg of DNA in TE (10mM Tris-Cl pH 8.0, 1mM EDTA); preferred 200 µl at ~100 ng/µl. Please provide DNA OD 260280 ratio (preferred 1.7-1.9) and send agarose picture with high mw genomic DNA, if available. Store at -20°C. Ship frozen on dry ice (preferred) or ice. It is recommended if DNA has undergone multiple freeze/thaw cycles that it not be submitted. Cultured Cells: We accept cultured cells from fibroblasts. Prefer two T25 cell flasks (one flask is acceptable) or suitable alternative at 80% confluence. Store at 2-8°C in tissue culture incubator up to 72 hours. Do not freeze. Please call ahead when sending prenatal samples. TEST CODES ASSOCIATED TESTS TURNAROUND TIMES 8884 DCMNext (ABCC9, ACTC1, ACTN2, ANKRD1, BAG3, CSRP3, DES, DMD, EYA4, FKTN, LAMA4, LAMP2, LDB3/ZASP, LMNA, MYBPC3, MYH6, MYH7, MYPN, NEXN, PLN, RAF1, RBM20, SCN5A, TCAP, TMPO, TNNC1, TNNI3, TNNT2, TPM1, TTN, TXNRD2, VCL) 6-8 weeks 8886 CMNext (ABCC9, ACTC1, ACTN2, ANKRD1, BAG3, CRYAB, CSRP3, DES, DMD, DSC2, DSG2, DSP, EMD, EYA4, FKTN, FXN, GATAD1, GLA, JPH2, JUP, LAMA4, LAMP2, LDB3/ZASP, LMNA, MYBPC3, MYH6, MYH7, MYL2, MYL3, MYOZ2, MYPN, NEXN, PKP2, PLN, PTPN11, RAF1, RBM20, RYR2, SCN5A, TCAP, TGFB3, TMEM43, TMPO, TNNC1, TNNI3, TNNT2, TPM1, TTR, TXNRD2, VCL) 6-8 weeks 8887 CMNext plus TTN 8-10 weeks 8910 CardioNext (ABCC9, ACTC1, ACTN2, AKAP9, ANK2, ANKRD1, BAG3, CACNA1C, CACNA2D1, CACNB2, CALM1, CASQ2, CAV3, CRYAB, CSRP3, DES, DMD, DSC2, DSG2, DSP, EMD, EYA4, FKTN, FXN, GATA4, GATAD1, GLA, GPD1L, HCN4, JAG1, JPH2, JUP, KCND3, KCNE1, KCNE2, KCNE3, KCNH2, KCNJ2, KCNJ5, KCNJ8, KCNQ1, LAMA4, LAMP2, LDB3/ZASP, LMNA, MYBPC3, MYH6, MYH7, MYL2, MYL3, MYOZ2, MYPN, NEXN, NKX2.5, PKP2, PLN, PTPN11, RAF1, RBM20, RYR2, SCN1B, SCN2B, SCN3B, SCN4B, SCN5A, SNTA1, TAZ, TBX1, TBX5, TBX20, TCAP, TGFB3, TMEM43, TMPO, TNNC1, TNNI3, TNNT2, TPM1, TRDN, TRPM4, TTR, TXNRD2, VCL) 8-10 weeks 8911 CardioNext plus TTN 10-12 weeks references 1. Hershberger RE, Morales A. Dilated Cardiomyopathy Overview. 2007 Jul 27 [Updated 2013 May 9]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. Available from: http://www.ncbi.nlm.nih.gov/books/ NBK1309/ 2. Adapted from Ackerman MJ, et al. HRS/EHRA Expert Consensus Statement on the State of Genetic Testing for the Channelopathies and Cardiomyopathies. Heart Rhythm. 2011 Aug;8(8):1308-39. 3. Brodt C, et al. Temporal relationship of conduction system disease and ventricular dysfunction in LMNA cardiomyopathy. J Card Fail. 2013. Apr;19(4):233-9. 50339.2574_v1 15 Argonaut, Aliso Viejo, CA 92656 Toll Free 866 262 7943 Fax 949 900 5501 ambrygen.com