DCMNext

DCMNextTM is a targeted panel for patients with dilated cardiomyopathy (DCM).  Often, DCM can be asymptomatic and sudden death is the first and only symptom. Therefore, genetic testing may be the most effective way of identifying at-risk individuals, or confirming a diagnosis.

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DCMNextTM is a targeted panel for patients with dilated cardiomyopathy (DCM).  Often, DCM can be asymptomatic and sudden death is the first and only symptom. Therefore, genetic testing may be the most effective way of identifying at-risk individuals, or confirming a diagnosis.

DCMNext is a next generation sequencing (NGS) and deletion/duplication panel of 36 genes associated with DCM: ABCC9, ACTC1, ACTN2, ANKRD1, BAG3, CSRP3, DES, DMD, EYA4, FKTN, LAMA4, LAMP2, LDB3/ZASP, LMNA, MYBPC3, MYH6, MYH7, MYPN, NEXN, NKX2.5, PLN, RAF1, RBM20, SCN5A, TAZ, TBX20, TCAP, TMPO, TNNC1, TNNI3, TNNT2, TPM1, TTN, TTR, TXNRD2 and VCL. These genes are also included in the comprehensive inherited cardiomyopathy (CMNextTM) and cardiovascular genetics (CardioNextTM) panels. 

Disease Name 
Dilated cardiomyopathy
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.  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.  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.

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).  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.

 

Genes Implicated in Non-Ischemic Dilated Cardiomyopathy

graph of genes implicated in dilated cardiomyopathy scn5a, myh7, m7h6, ttn, lmna

Testing Benefits & Indication 
  • 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 a specific cardiac genotype, or underlying conditions like Duchenne muscular dystrophy and Danon disease
  • Confirm diagnosis and identify inherited mutation following a sudden death with autopsy findings that indicate DCM.
  • 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

Test Description 

DCMNext includes 36 genes that cause DCM (listed earlier). These genes are also included in the comprehensive cardiomyopathy (CMNext) and cardiovascular genetics (CardioNext) panels. 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. Sanger sequencing is performed for any regions missing or with insufficient read depth coverage for reliable heterozygous variant detection. Suspect variant calls are verified by Sanger sequencing.  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 35 genes is performed utilizing a targeted chromosomal microarray (for all except TXNRD2).

Mutation Detection Rate 

30-40% of patients with non-ischemic DCM have a mutation in one of the DCMNext genes (clinical sensitivity).  DCMNext can detect >99.9% of described mutations in the included genes, when present (analytic sensitivity).

Specimen Requirements 

Complete specimen requirements are available here or by downloading the PDF found above on this page.

Turnaround Time 
TEST CODE TEST NAME TURNAROUND TIME (Weeks)
8884 DCMNextTM 4-5 
8886 CMNextTM 4-5 
8887 CMNext + TTN 4-5 
8910 CardioNext 4-5 
8911 CardioNext + TTN 4-5 
9520 CustomNext-Cardio
Up to 85 cardiovascular genes of your choice
4-5 weeks

 

Specialty 
Genes 
ABCC9
ACTC1
ACTN2
ANKRD1
BAG3
CSRP3
DES
DMD
EYA4
FKTN
LAMA4
LAMP2
LDB3/ZASP
LMNA
MYBPC3
MYH6
MYH7
MYPN
NEXN
NKX2.5
PLN
RAF1
RBM20
SCN5A
TAZ
TBX20
TCAP
TMPO
TNNC1
TNNI3
TNNT2
TPM1
TTN
TTR
TXNRD2
VCL
Tests 
References 
  1. 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.
  2. 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. 
  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.