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Test Code DMDZ DMD Gene, Full Gene Analysis, Varies


Ordering Guidance


Targeted testing for familial variants (also called site-specific or known mutations testing) is available for variants identified in the DMD gene. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.

 

Testing for the DMD gene as a customized panel is available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.



Additional Testing Requirements


For cord blood specimens: Maternal cell contamination (MCC) studies are available. Order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on both the cord blood and maternal specimens under separate order numbers. Cord blood testing will proceed without MCC studies, but results may be compromised if MCC is present.



Specimen Required


Patient Preparation: A previous bone marrow stem cell transplant from an allogenic donor will interfere with testing. For information about testing patients who have received a hematopoietic stem cell transplant, call 800-533-1710.

 

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube: Lavender top (EDTA) or yellow top (ACD)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 4 days/Frozen 4 days

Additional Information:

1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for specimens received after 4 days, and DNA yield will be evaluated to determine if testing may proceed.

2. To ensure minimum volume and concentration of DNA are met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.

 

Specimen Type: Cord blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send cord blood specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 4 days/Frozen 4 days

Additional Information:

1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for specimens received after 4 days, and DNA yield will be evaluated to determine if testing may proceed.

2. To ensure minimum volume and concentration of DNA are met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.

3. While a properly collected cord blood sample may not be at risk for maternal cell contamination, unanticipated complications may occur during collection. Therefore, maternal cell contamination studies are recommended to ensure the test results reflect that of the patient tested and are available at an additional charge. Order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.

 

Specimen Type: Saliva

Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.

Supplies: Saliva Swab Collection Kit (T786)

Specimen Volume: 1 Swab

Collection Instructions: Collect and send specimen per kit instructions.

Specimen Stability Information: Ambient (preferred) 30 days/Refrigerated 30 days

Additional Information: Saliva specimens are acceptable but not recommended. Due to lower quantity/quality of DNA yielded from saliva, some aspects of the test may not perform as well as DNA extracted from a whole blood sample. When applicable, specific gene regions that were unable to be interrogated will be noted in the report. Alternatively, additional specimen may be required to complete testing.

 

Specimen Type: Extracted DNA

Container/Tube:

Preferred: Screw Cap Micro Tube, 2 mL with skirted conical base

Acceptable: Matrix tube, 1 mL

Collection Instructions:

1. The preferred volume is at least 100 mcL at a concentration of 75 ng/mcL.

2. Include concentration and volume on tube.

Specimen Stability Information: Frozen (preferred) 1 year/Ambient/Refrigerated

Additional Information: DNA must be extracted in a CLIA-certified laboratory or equivalent and must be extracted from a specimen type listed as acceptable for this test (including applicable anticoagulants). Our laboratory has experience with Chemagic, Puregene, Autopure, MagnaPure, and EZ1 extraction platforms and cannot guarantee that all extraction methods are compatible with this test. If testing fails, one repeat will be attempted, and if unsuccessful, the test will be reported as failed and a charge will be applied. If applicable, specific gene regions that were unable to be interrogated due to DNA quality will be noted in the report.

 

 

PRENATAL SPECIMENS

Due to its complexity, consultation with the laboratory is required for all prenatal testing; call 800-533-1710 to speak to a genetic counselor.

 

Specimen Type: Amniotic fluid

Container/Tube: Amniotic fluid container

Specimen Volume: 20 mL

Specimen Stability Information: Ambient (preferred) <24 hours/Refrigerated <24 hours

Additional Information: Specimen will only be tested after culture.

1. Specimens are preferred to be received within 24 hours of collection. Culture and extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.

2. A separate culture charge will be assessed under CULAF / Culture for Genetic Testing, Amniotic Fluid. An additional 2 to 3 weeks are required to culture amniotic fluid before genetic testing can occur.

3. All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.

 

Specimen Type: Confluent cultured amniocytes

Container/Tube: T-25 flask

Specimen Volume: 2 Full flasks

Collection Instructions: Submit confluent cultured amniocytes from another laboratory

Specimen Stability Information: Ambient (preferred) <24 hours/Refrigerated <24 hours

Additional Information:

1. Specimens are preferred to be received within 24 hours of collection. Culture and extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.

2. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing.

3. All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.

 

Specimen Type: Chorionic villi

Container/Tube: 15-mL tube containing 15 mL of transport media

Specimen Volume: 20 mg

Specimen Stability Information: Ambient (preferred) <24 hours/Refrigerated <24 hours

Additional Information: Specimen will only be tested after culture.

1. Specimens are preferred to be received within 24 hours of collection. Culture and extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.

2. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks are required to culture fibroblasts before genetic testing can occur.

3. All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.

 

Specimen Type: Cultured chorionic villi

Container/Tube: T-25 flasks

Specimen Volume: 2 Full flasks

Collection Instructions: Submit confluent cultured cells from another laboratory

Specimen Stability Information: Ambient (preferred) <24 hours/Refrigerated <24 hours

Additional Information:

1. Specimens are preferred to be received within 24 hours of collection. Culture and extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.

2. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing.

3. All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.


Forms

1. New York Clients-Informed consent is required.

Document on the request form or electronic order that a copy is on file.

The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing (Spanish) (T826)

2. Molecular Genetics: Neurology Patient Information

3. If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.

Useful For

Establishing a molecular diagnosis for patients with Duchenne muscular dystrophy and Becker muscular dystrophy

 

Identifying variants within DMD known to be associated with Duchenne muscular dystrophy or Becker muscular dystrophy, allowing for predictive testing of at-risk family members

Genetics Test Information

This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in one gene associated with Duchenne muscular dystrophy and Becker muscular dystrophy: DMD. See Method Description for additional details.

 

Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, recurrence risk assessment, familial screening, and genetic counseling for Duchenne muscular dystrophy and Becker muscular dystrophy.

Method Name

Sequence Capture and Targeted Next-Generation Sequencing (NGS) followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing

Reporting Name

DMD Gene, Full Gene Analysis

Specimen Type

Varies

Specimen Minimum Volume

See Specimen Required

Specimen Stability Information

Specimen Type Temperature Time
Varies Varies

Reject Due To

  All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Clinical Information

Dystrophinopathies are X-linked disorders due to disease-causing variants in the DMD gene. DMD encodes for dystrophin, an integral muscle protein that plays a critical role in muscle membrane stability. A loss or reduction of dystrophin protein results in muscle degeneration over time.

 

Duchenne muscular dystrophy (DMD) is a more severe form of dystrophinopathy characterized by proximal muscle weakness beginning before age 5 years. Affected individuals typically have pseudohypertrophy of the calf muscles and exhibit toe-walking, waddling gait, and the Gower sign (climbing up the legs with hands when rising from a seated position on the floor). Initial symptoms are followed by dramatic progression of weakness leading to loss of ambulation by age 11 or 12 years. Additional associated clinical symptoms include developmental delay, pulmonary disease, cardiomyopathy, scoliosis, and joint contractures. Death is often caused by cardiac failure in the second to third decade. The allelic Becker muscular dystrophy (BMD) has a similar presentation, although age of onset is later with a slower clinical course and milder symptoms. Cardiac involvement can be the only feature, and patients are often ambulatory into their thirties or later. Management guidelines are available for DMD, and several US Food and Drug Administration-approved variant specific therapies are available and emerging, including exon skipping therapies and gene therapy.

 

As an X-linked condition, dystrophinopathies typically affect 46,XY individuals or individuals assigned male at birth (AMAB); however, heterozygous 46,XX individuals with a disease-causing DMD variant may present with neuromuscular or cardiac symptoms, typically milder than those seen in 46,XY individuals. Approximately two-thirds of AMABs with a disease-causing DMD variant inherited the variant from a heterozygous 46,XX parent, while one-third of individuals with DMD have the condition as result of a de novo variant. In such cases, the recurrence risk is reduced, but not eliminated, as DMD is associated with germline mosaicism at an estimated frequency of 15%.

 

Disease-causing DMD variants consist primarily of large deletions and duplications. Approximately 70% of patients have intragenic deletions, and approximately 20% have intragenic duplications. Less frequently, DMD and BMD result from other types of variants such as missense, nonsense, splice site and small deletions and duplications. This assay detects both large intragenic deletions and duplications along with small deletions and duplications and single nucleotide variants and can be utilized for diagnosis of dystrophinopathies, carrier screening, and follow up for positive newborn screening.

Reference Values

An interpretive report will be provided.

Interpretation

All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Cautions

Clinical Correlations:

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

If testing was performed because of a clinically significant family history, it is often useful to first test an affected family member. Detection of a reportable variant in an affected family member would allow for more informative testing of at-risk individuals.

 

To discuss the availability of additional testing options or for assistance in the interpretation of these results, contact Mayo Clinic Laboratories genetic counselors at 800-533-1710.

 

Technical Limitations:

Next-generation sequencing may not detect all types of genomic variants. In rare cases, false-negative or false-positive results may occur. The depth of coverage may be variable for some target regions; assay performance below the minimum acceptable criteria or for failed regions will be noted. Given these limitations, negative results do not rule out the diagnosis of a genetic disorder. If a specific clinical disorder is suspected, evaluation by alternative methods can be considered.

 

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. Confirmation of select reportable variants will be performed by alternate methodologies based on internal laboratory criteria.

 

This test is validated to detect 95% of deletions up to 75 base pairs (bp) and insertions up to 47 bp. Deletions-insertions (delins) of 40 or more bp, including mobile element insertions, may be less reliably detected than smaller delins.

 

This analysis targets single and multi-exon deletions/duplications; however, in some instances single exon resolution cannot be achieved due to isolated reduction in sequence coverage or inherent genomic complexity. Balanced structural rearrangements (such as translocations and inversions) may not be detected.

 

This test is not designed to detect low levels of mosaicism or to differentiate between somatic mutations and germline variants. If there is a possibility that any detected variant is somatic, additional testing may be necessary to clarify the significance of results.

 

For detailed information regarding gene specific performance and technical limitations, see Method Description or contact a laboratory genetic counselor.

 

If the patient has had an allogeneic hematopoietic stem cell transplant or a recent non-leukocyte reduced blood transfusion, results may be inaccurate due to the presence of donor DNA. Call Mayo Clinic Laboratories for instructions regarding testing patients who have received a bone marrow transplant.

 

Reclassification of Variants:

Currently, it is not standard practice for the laboratory to systematically review previously classified variants on a regular basis. The laboratory encourages healthcare professionals to contact the laboratory at any time to learn how the classification of a particular variant may have changed over time. Due to broadening genetic knowledge, it is possible that the laboratory may discover new information of relevance to the patient. Should that occur, the laboratory may issue an amended report.

 

Variant Evaluation:

Evaluation and categorization of variants are performed using published American College of Medical Genetics and Genomics and the Association for Molecular Pathology recommendations as a guideline.(1) Other gene-specific guidelines may also be considered. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. Variants classified as benign or likely benign are not reported.

 

Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and periodic updates to these tools may cause predictions to change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgment.

 

Rarely, incidental or secondary findings may implicate another predisposition or presence of active disease. These findings will be carefully reviewed to determine whether they will be reported.

Method Description

Next-generation sequencing (NGS) and/or Sanger sequencing are performed to test for the presence of variants in coding regions, and intron/exon boundaries of the gene analyzed, as well as some other regions that have known disease-causing variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for deletion-insertions (delins) less than 40 base pairs (bp), above 95% for deletions up to 75 bp and insertions up to 47 bp. NGS and/or a polymerase chain reaction-based quantitative method is performed to test for the presence of deletions and duplications in the gene analyzed.

 

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences.(Unpublished Mayo method)

 

The reference transcript for DMD gene is NM_004006.2. Reference transcript numbers may be updated due to transcript re-versioning. Always refer to the final patient report for gene transcript information referenced at the time of testing.

 

Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.

Day(s) Performed

Varies

Report Available

21 to 35 days

Specimen Retention Time

Whole blood: 28 days (if available); Saliva: 30 days (if available); Extracted DNA: 3 months

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information

81408

LOINC Code Information

Test ID Test Order Name Order LOINC Value
DMDZ DMD Gene, Full Gene Analysis 22075-6

 

Result ID Test Result Name Result LOINC Value
617533 Test Description 62364-5
617534 Specimen 31208-2
617535 Source 31208-2
617536 Result Summary 50397-9
617537 Result 82939-0
617538 Interpretation 69047-9
618177 Additional Results 82939-0
617539 Resources 99622-3
617540 Additional Information 48767-8
617541 Method 85069-3
617542 Genes Analyzed 48018-6
617543 Disclaimer 62364-5
617544 Released By 18771-6

Testing Algorithm

Skin biopsy:

If skin biopsy is received, fibroblast culture will be added at an additional charge. If viable cells are not obtained, the client will be notified.

 

Prenatal specimens:

If an amniotic fluid specimen is received, an amniotic fluid culture will be performed at an additional charge.

If chorionic villi, cultured chorionic villi, or cultured amniocyte specimen is received, a fibroblast culture will be performed at an additional charge.

 

For any prenatal specimen that is received, maternal cell contamination testing will be performed at an additional charge.

 

Cord blood:

For cord blood specimens that have an accompanying maternal blood specimen, maternal cell contamination studies will be performed at an additional charge.

 

For information see Neuromuscular Myopathy Testing Algorithm.

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
CULFB Fibroblast Culture for Genetic Test Yes No
CULAF Amniotic Fluid Culture/Genetic Test Yes No
MATCC Maternal Cell Contamination, B Yes No