Test Id : PMPDD

For information see Hereditary Peripheral Neuropathy Diagnostic Algorithm

Patient Preparation: A previous hematopoietic stem cell transplant from an allogenic donor will interfere with testing. For instructions for 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:

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

Acceptable: None

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 is 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)

Acceptable: None

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send 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 is met, the preferred volume of blood 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.

4. Order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.

Specimen Type: Extracted DNA

Container/Tube:

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

Acceptable: Matrix tube, 1mL

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.

• Informed Consent for Genetic Testing
• Hereditary Peripheral Neuropathy Diagnostic Algorithm
• Molecular Genetics: Neurology Patient Information
• Informed Consent for Genetic Testing (Spanish)

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 in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T576)

2. Molecular Genetics: Neurology Patient Information in Special Instructions

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

See Specimen Required

Diagnosis of Charcot-Marie-Tooth type 1A or hereditary neuropathy with liability to pressure palsies

This test assesses for large deletions and duplications only.

For information see Hereditary Peripheral Neuropathy Diagnostic Algorithm

This test is appropriate as a first-tier test for individuals with clinical features suggestive of Charcot-Marie-Tooth type 1A (CMT1A) and/or hereditary neuropathy with liability to pressure palsies (HNPP).

Charcot-Marie-Tooth type 1A is a dominantly inherited disease characterized by progressive distal muscle weakness and atrophy, sensory loss, and slow nerve conduction velocity starting early in life. Duplications of the PMP22 gene are associated with CMT1A and are thought to account for 45%-50% of all CMT and up to 80% of demyelinating CMT.

Deletions of PMP22 are associated with HNPP, a dominantly inherited disease resulting in peripheral neuronal demyelination. HNPP is characterized clinically by recurrent focal motor and sensory neuropathy in a single nerve that can manifest as numbness, muscular weakness, and atrophy. Deletions of PMP22 are thought to account for up 80% of HNPP.

An interpretive report will be provided.

All detected alterations 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.

In addition to disease-related probes, the multiplex ligation-dependent probe amplification technique utilizes probes localized to other chromosomal regions as internal controls. In certain circumstances, these control probes may detect other diseases or conditions for which this test was not specifically intended. Results of the control probes are not normally reported. However, in cases where clinically relevant information is identified, the ordering physician will be informed of the result and provided with recommendations for any appropriate follow-up testing.

This test may not detect deletions/duplications present in very low levels of mosaicism.

Rare alterations (ie, polymorphisms) exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.

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

1. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-424

2. van Paassen BW, van der Kooi AJ, van Spaendonck-Zwarts KY, Verhamme C, Baas F, de Visser M. PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies. Orphanet J Rare Dis. 2014;9:38

3. Li J, Parker B, Martyn C, Natarajan C, Guo J. The PMP22 gene and its related diseases. Mol Neurobiol. 2013;47(2):673-698

4. Bird TD. Charcot-Marie-Tooth Hereditary Neuropathy Overview. In: Adam MP, Feldman J, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 1998. Updated August 1, 2024. Accessed January 16, 2025. Available at www.ncbi.nlm.nih.gov/books/NBK1358/

5. Chen L, Zhang H, Li C, Yang N, Wang J, Liang J. Literature review of clinical analysis of hereditary neuropathy with liability to pressure palsies. J Neurol. 2024;272(1):41. doi:10.1007/s00415-024-12839-7

6. Chrestian N. Hereditary Neuropathy with Liability to Pressure Palsies. In: Adam MP, Feldman J, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 1998. Updated August 27, 2020. Accessed January 16, 2025. Available at www.ncbi.nlm.nih.gov/books/NBK1392/

7. Martinez Thompson JM, Klein CJ. Thirty Years Later, Case Closed: A Case of PMP22 Triplication From Anticipation. Mayo Clin Proc. 2016;91(5):687-688. doi:10.1016/j.mayocp.2015.12.019

8. Pisciotta C, Bertini A, Tramacere I, et al. Clinical spectrum and frequency of Charcot-Marie-Tooth disease in Italy: Data from the National CMT Registry. Eur J Neurol. 2023;30(8):2461-2470. doi:10.1111/ene.15860

9. Weterman MA, van Ruissen F, de Wissel M, et al. Copy number variation upstream of PMP22 in Charcot-Marie-Tooth disease. Eur J Hum Genet. 2010;18(4):421-428. doi:10.1038/ejhg.2009.186

10. Zhang F, Seeman P, Liu P, et al. Mechanisms for nonrecurrent genomic rearrangements associated with CMT1A or HNPP: rare CNVs as a cause for missing heritability. Am J Hum Genet. 2010;86(6):892-903. doi:10.1016/j.ajhg.2010.05.001

Multiple ligation-dependent probe amplification (MLPA) is utilized to test for the presence of large deletions and duplications within the PMP22 gene.(Unpublished Mayo method)

Varies

• Authorized users can sign in to Test Prices for detailed fee information.
• Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
• Prospective clients should contact their account representative. For assistance, contact Customer Service.

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.

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