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Myofibrillar Myopathy via the DES Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
8575 DES 81405 81405,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8575DES81405 81405,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Myofibrillar myopathy (MFM) refers to a genetically heterogeneous group of disorders sharing a homogeneous morphological pattern and, most often, onset of clinical symptoms in adulthood. Stained with trichome, abnormal muscle fibers are seen containing hyaline structures and vacuoles that contain membrane fragments from disintegrated sarcomeric Z disc and myofibrils (Selcen et al. Brain 127:439-451, 2004). With electron microscopy, affected muscle fibers reveal progressive degeneration of myofibrils beginning at the Z-disk. Immunohistochemical staining of the structurally abnormal fibers reveals abnormal expression and accumulation of several proteins, including myotilin, desmin, alpha-B crystalline, dystrophin, and β-amyloid precursor protein (Selcen et al. 2004). Clinically, patients present in adulthood with proximal and distal weakness and in some cases with cardiomyopathy. Dilated cardiomyopathy is present in 15-30% of desmin-related MFM (Selcen and Engel. GeneReviews 2010). Cardiac manifestations include conduction blocks, arrhythmias, and restrictive heart failure (Li et al. Circulation 100:461-464, 1999; Goldfarb et al. Nat Genet 19:402-403, 1998; Dalakas et al. N Eng J Med 342:770-780, 2000).

Genetics

Desmin, a cytoskeletal protein that functions as an attachment between the terminal Z disc and membrane-associated proteins (Tidball, Exp Cell Res 199:206-212, 1992), is expressed in smooth, cardiac, and skeletal muscles. Desmin-related myofibrillar myopathy (OMIM 601419) is inherited as an autosomal dominant disorder. Approximately 25% of affected individuals have an affected parent, but the proportion of de novo variants is unknown (Selcen and Engel, 2010). Other genes involved with MFM include MYOT, FLNC, LDB3, CRYAB, and BAG3.

Clinical Sensitivity - Sequencing with CNV PGxome

Among a cohort of 80 MFM patients diagnosed at the Mayo Clinic, only 46% were found to have variants in one of the six known causative genes (Selcen and Engel, 2010). The relative frequencies of variants found in the Mayo Clinic cohort were LDB3 (14%), MYOT (13%), DES (8%), FLNC (4%), BAG3 (4%), and CRYAB (3%). Among eight other families with dominantly inherited MFM and two patients with sporadic disease, Dalakas et al. (2000) found variants in four of the families and in one of the sporadic cases. Of the twelve total affected individuals with DES variants in this study, seven had cardiomyopathy. MFM appears to be a genetically heterogeneous disorder, and the clinical sensitivity for testing any of the known genes is likely low.

Testing Strategy

This test provides full coverage of all coding exons of the DES gene 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 full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Patients with clinical features consistent with myofibrillar myopathy, demonstrated autosomal dominant inheritance, and a muscle biopsy with characteristic immunohistochemical and ultrastructural features. Individuals with idiopathic cardiomyopathy.

Gene

Official Gene Symbol OMIM ID
DES 125660
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Myofibrillar Myopathy, Desmin-Related AR, AD 601419

Related Tests

Name
Comprehensive Cardiology Panel
Sudden Cardiac Arrest Panel

Citations

  • Dalakas, M. C., et.al. (2000). "Desmin myopathy, a skeletal myopathy with cardiomyopathy caused by mutations in the desmin gene." N Engl J Med 342(11): 770-80. PubMed ID: 10717012
  • Duygu Selcen, Andrew G Engel (2010). "Myofibrillar Myopathy."
  • Goldfarb, L. G., et.al. (1998). "Missense mutations in desmin associated with familial cardiac and skeletal myopathy." Nat Genet 19(4): 402-3. PubMed ID: 9697706
  • Li, D., et.al. (1999). "Desmin mutation responsible for idiopathic dilated cardiomyopathy." Circulation 100(5): 461-4. PubMed ID: 10430757
  • Selcen D, Ohno K, Engel AG. 2004. Myofibrillar myopathy: clinical, morphological and genetic studies in 63 patients. Brain 127(Pt 2): 439-451. PubMed ID: 14711882
  • Tidball, J. G. (1992). "Desmin at myotendinous junctions." Exp Cell Res 199(2): 206-12. PubMed ID: 1544366

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

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View Ordering Instructions

1) Select Test Method (Platform)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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