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Dystrophinopathy via the DMD Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
1773 DMD 81408 81408,81161 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
1773DMD81408 81408,81161 $990 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

Testing run on PG-Select capture probes does not include exome-wide CNV analysis. Reflex is available to PGxome or an exome-based panel, or you can use this gene list to create a custom panel (click here).

Click here for costs to reflex to whole PGxome.

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

The dystrophinopathies include Duchenne muscular dystrophy (DMD, OMIM 310200), Becker muscular dystrophy (BMD, OMIM 300376), and dilated cardiomyopathy, type 3B (CMD3B, OMIM 302045).

Duchenne muscular dystrophy is the most common form of congenital muscular dystrophy in all ethnic groups. DMD presents in affected boys in early childhood with difficulty walking and climbing stairs, progressive proximal weakness, pseudohypertrophy of the calves, and greatly elevated serum creatine phosphokinase (CK) levels (Darras et al. 2011). Patients become wheelchair dependent by age 13. Dilated cardiomyopathy and congestive heart failure occur in nearly all patients by their late teens or early 20s. DMD muscle biopsies show a dystrophic process with fibrosis and fatty infiltration. Dystrophin protein content in DMD patients is less than 5% of controls when measured by Western blot or immunohistochemistry (Hoffman et al. 1988).

Becker muscular dystrophy is a relatively mild form of dystrophinopthy with later onset of proximal weakness and preservation of ambulation into the third decade of life. The minimum age for wheelchair dependency in BMD is age 16. As in DMD, cardiomyopathy is a significant cause of morbidity, however, serum CK levels are less elevated than in DMD (Zatz et al. 1991). Dystrophin protein content in BMD patients varies from 20% of control levels to normal levels when measured by Western blot or immunohistochemistry (Hoffman et al. 1988).

Both DMD and BMD can be associated with intellectual deficits, specifically involving working memory and executive function (Darras et al. 2011).

DMD-related cardiomyopathy in the absence of skeletal muscle disease is a less common form of dystrophinopathy which presents in affected males between 20 and 40 years of age and later in carrier females (Beggs 1997). In some mild BMD patients, cardiomyopathy can be the presenting feature (Towbin 1998).

Females who are heterozygous for a DMD causative mutation are at risk for dilated cardiomyopathy and 70% have slightly elevated CK (Schade van Westrum et al. 2011). Carriers may also present with a myopathy resembling limb-girdle muscular dystrophy (Moser and Emery 1974).

Genetics

The dystrophinopathies are inherited as X-linked recessive disorders, and approximately one-third of mothers who have a son with dystrophinopathy have no family history. Heterozygous female carriers are at increased risk for dilated cardiomyopathy. The extent of skeletal muscle involvement in carriers is dependent upon the level of skewed X-chromosome inactivation.

The DMD gene is located at Xp21 and occupies about 1.5% of the entire X chromosome. Approximately two-thirds of the mutations in DMD patients are deletions of one or more exons in the DMD gene. The occurrence of deletions is slightly higher in BMD patients. Duplications are found in approximately 10% of DMD patients and 20% of BMD patients. In general, in-frame deletions, which preserve partial functional dystrophin protein, are correlated with a milder (BMD) clinical phenotype (Monaco et al. 1988; Aartsma-Rus et al. 2006).

Mutations detectable by sequence analysis are found in approximately one-third of DMD cases and in approximately 20% of BMD cases. In DMD cases, the vast majority of these mutations result in premature protein termination whereas missense mutations are rare (http://www.LOVD.nl/DMD).

DMD (OMIM 300377) encodes dystrophin, a large structural protein that binds sarcoplasmic actin at its amino end and beta dystroglycan at its carboxyl end, thus bridging the cytoskeleton to the dystroglycan-associated glycoprotein complex at the sarcolemma (Barresi and Campbell 2006).

Clinical Sensitivity - Sequencing with CNV PG-Select

Mutations detectable by sequence analysis are found in approximately one-third of DMD cases and in approximately 20% of BMD cases. In DMD cases, the vast majority of these mutations result in premature protein termination whereas missense mutations are rare (http://www.LOVD.nl/DMD).

Approximately two-thirds of the mutations in DMD patients are deletions of one or more exons in the DMD gene. The occurrence of deletions is slightly higher in BMD patients. Duplications are found in approximately 10% of DMD patients and 20% of BMD patients. In general, in-frame deletions, which preserve partial functional dystrophin protein, are correlated with a milder (BMD) clinical phenotype (Monaco et al. 1988; Aartsma-Rus et al. 2006).

Testing Strategy

This test provides full coverage of all coding exons of the DMD gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

1. Males with a clinical diagnosis of DMD/BMD.

2. Males with symptoms of DMD/BMD (A waddling gait and difficulty climbing stairs, Gower sign, elevated CPK).

3. Male/Females with a negative DMD/BMD test by multiplex PCR, MLPA, or Southern blot.

4. Males/Females with previous DMD/BMD test result with unclear del/dup size and boundary.

5. Females at risk of being a carrier (Previous child or a family history of DMD/BMD).

Gene

Official Gene Symbol OMIM ID
DMD 300377
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
Comprehensive Cardiology Panel

Citations

  • Aartsma-Rus A, Deutekom JCT Van, Fokkema IF, Ommen G-JB Van, Dunnen JT Den. 2006. Entries in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation types and paradoxical cases that confirm the reading-frame rule. Muscle Nerve 34: 135–144. PubMed ID: 16770791
  • Barresi R, Campbell K. 2006. Dystroglycan: from biosynthesis to pathogenesis of human disease. J. Cell Sci. 119:199-207. PubMed ID: 16410545
  • Beggs AH. 1997. Dystrophinopathy, The Expanding Phenotype Dystrophin Abnormalities in X-Linked Dilated Cardiomyopathy. Circulation 95: 2344–2347. PubMed ID: 9170393
  • Darras BT, Miller DT, Urion DK. 2011. Dystrophinopathies. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301298
  • Hoffman EP, Fischbeck KH, Brown RH, Johnson M, Medori R, Loike JD, Harris JB, Waterston R, Brooke M, Specht L. 1988. Characterization of dystrophin in muscle-biopsy specimens from patients with Duchenne’s or Becker’s muscular dystrophy. N. Engl. J. Med. 318: 1363–1368. PubMed ID: 3285207
  • Leiden Open Variation Database- DMD.
  • Monaco AP, Bertelson CJ, Liechti-Gallati S, Moser H, Kunkel LM. 1988. An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus. Genomics 2: 90–95. PubMed ID: 3384440
  • Moser H, Emery AE. 1974. The manifesting carrier in Duchenne muscular dystrophy. Clin. Genet. 5: 271–284. PubMed ID: 4854942
  • Schade van Westrum SM, Hoogerwaard EM, Dekker L, Standaar TS, Bakker E, Ippel PF, Oosterwijk JC, Majoor-Krakauer DF, Essen AJ van, Leschot NJ, Wilde AAM, Haan RJ de, et al. 2011. Cardiac abnormalities in a follow-up study on carriers of Duchenne and Becker muscular dystrophy. Neurology 77: 62–66. PubMed ID: 21700587
  • Towbin JA. 1998. The role of cytoskeletal proteins in cardiomyopathies. Curr. Opin. Cell Biol. 10: 131–139. PubMed ID: 9484605
  • Zatz M, Rapaport D, Vainzof M, Passos-Bueno MR, Bortolini ER, Pavanello R de C, Peres CA. 1991. Serum creatine-kinase (CK) and pyruvate-kinase (PK) activities in Duchenne (DMD) as compared with Becker (BMD) muscular dystrophy. J. Neurol. Sci. 102: 190–196. PubMed ID: 2072118

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

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