Oxford Molecular Genetics Laboratory
Genetics Laboratories, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LE
www.ouh.nhs.uk/geneticslab
Dilated Cardiomyopathy: 36 Gene Panel
INTRODUCTION
Dilated cardiomyopathy (DCM) is a myocardial disorder defined by the presence of a dilated and poorly functioning left ventricle, meaning the heart
is unable to pump blood efficiently. Idiopathic DCM is estimated to affect ~1 in 2,500 adults and often presents with reduced exercise tolerance or
dyspnoea. More severe signs of heart failure may ensue in some cases if left untreated. Some affected individuals also have cardiac conduction
defects. Familial DCM is usually inherited in an autosomal dominant pattern with incomplete penetrance. Mutations in >30 genes, including those
that encode protein components of the sarcomere and Z-disc, are known to predispose to the disorder.
The Oxford Medical Genetics Laboratory provides molecular genetic testing for 36 DCM-relevant genes (see table below). The multi-gene panel
includes not only genes primarily related to DCM, but also genes more closely related to hypertrophic cardiomyopathy (HCM) and arrhythmogenic
right ventricular cardiomyopathy (ARVC), both of which may clinically overlap with DCM. The overall clinical sensitivity for probands screened on this
panel is 20-30%.
Gene
Primary Related Disorders
Gene
Primary Related Disorders
ACTC1
ACTN2
ANKRD1
BAG3
CRYAB
CSRP3
DES
DMD
DSC2
DSG2
DSP
FHL1
FHL2
FLNC
GLA
JUP
LAMP2
LMNA
DCM, HCM, LVNC
DCM, HCM, LVNC
HCM, DCM
DCM, myofibrillar myopathy
DCM, skeletal myopathy.
HCM
ARVC, skeletal myopathy
D/BMD, X-linked DCM
ARVC
ARVC
ARVC, Carvajal syndrome, DCM
HCM, skeletal myopathy
DCM
HCM, myofibrillar myopathy
Anderson-Fabry disease
ARVC, Naxos syndrome
Danon’s disease
DCM, skeletal myopathy, other laminopathies
MYBPC3
MYH7
MYL2
MYL3
PKP2
PLN
PRKAG2
RBM20
SCN5A
TAZ
TMEM43
TNNC1
TNNI3
TNNT2
TPM1
TTN
TTR
VCL
HCM, LVNC
DCM, HCM, LVNC, RCM
HCM
HCM
ARVC
ARVC, DCM, HCM
HCM, WPW
DCM
Brugada syndrome, DCM
Barth syndrome
ARVC
DCM, HCM
DCM, HCM, RCM
DCM, HCM, LVNC, RCM
DCM, HCM, LVNC
DCM
Amyloidosis
DCM
DCM: dilated cardiomyopathy. D/BMD: Duchenne and Becker muscular dystrophies. HCM: hypertrophic cardiomyopathy.
LVNC: left ventricular non-compaction. RCM: restrictive cardiomyopathy. WPW: Wolff-Parkinson-White syndrome.
REFERRAL PROCEDURE
•
Diagnostic referrals are accepted for probands with a suspected or confirmed diagnosis of DCM.
o
o
o
•
Family test referrals are only accepted from Clinical Genetics specialists.
o
o
•
•
This multi-gene panel may also be appropriate for probands with left ventricular non-compaction (LVNC) or an undefined genetic cardiomyopathy.
Referrals are accepted from Cardiology, Clinical Genetics and Consultants from other relevant medical specialities.
Clinical information and details of relevant family history should be provided with all referrals either on the original request form or on a separate
pre-referral form (DCM pre-referral form).
Referrals for affected family members (i.e. segregation analysis) must be accompanied by appropriate clinical information.
Referrals for unaffected family members will only be considered for variants with clear evidence for pathogenicity.
Clinical advice is available from Dr Edward Blair, Consultant Clinical Geneticist, at the Churchill Hospital (Ed.Blair@ouh.nhs.uk).
Further information about the test can be obtained from the laboratory (OxfordCardiac@nhs.net).
SAMPLE REQUIREMENTS
•
•
This analysis requires >4 μg of DNA at >30 ng / μl.
DNA from formalin-fixed paraffin-embedded (FFPE) tissue may be suitable.
o
o
>300 ng (preferably >1,000 ng) at >30 ng / μl is required.
Total gene coverage may be lower due to the poor quality of DNA obtained from FFPE tissue.
STRATEGY AND TECHNICAL INFORMATION
•
Diagnostic Screens:
o
o
Gene target enrichment is undertaken using Agilent’s HaloPlex Target Enrichment System.
Libraries are sequenced on an Illumina MiSeq Desktop Sequencer.

o
o
o
•
This will involve sequence data generation in-house or by the High Throughput Genomics Group at the Wellcome Trust Centre for Human
Genetics, Oxford.
Sequence data are analysed on a custom-designed bioinformatic pipeline.
Where possible, regions of interest (ROIs) in the following genes are 100% covered either by >30 reads or by Sanger sequencing: DSP, LMNA,
SCN5A.
Coverage of ROIs in the remaining genes varies, but is typically 85–100% at >30 reads.
Family Tests:
o
Familial variants are targeted for analysis by Sanger sequencing of the relevant exon, with DNA from a family member used as a positive control
where possible.
TARGET REPORTING TIMES
•
•
•
Diagnostic screens:
Family tests:
Urgent analysis:
60-80 working days
10 working days
Please contact the laboratory.
PRICING
Please see the current price list on the Oxford Genetics Laboratories Molecular Genetics page.
N.B. Details are correct for the date of printing only. Updated: 12/10/2015.