Test Code IMSNP Inherited Motor and Sensory Neuropathy Gene Panel, Varies
Ordering Guidance
First tier testing for a diagnosis of Charcot-Marie-Tooth disease type 1 is available; order PMPDD / PMP22 Gene, Large Deletion/Duplication Analysis, Varies.
Targeted testing for familial variants (also called site-specific or known variants testing) is available for the genes on this panel. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.
Customization of this panel and single gene analysis for any gene present on this panel are available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.
Shipping Instructions
Specimen preferred to arrive within 96 hours of collection.
Specimen Required
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. For instructions for testing patients who have received a bone marrow transplant, call 800-533-1710.
Specimen Type: Whole blood
Container/Tube: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Any anticoagulant
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)/Refrigerated
Additional Information: 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.
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.
Secondary ID
617584Useful For
Establishing a molecular diagnosis for patients with hereditary motor and sensory neuropathy (HMSN) or Charcot-Marie-Tooth (CMT) disease
Identifying variants within genes known to be associated with HMSN or CMT disease, allowing for predictive testing of at-risk family members
Special Instructions
Method Name
Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing
Reporting Name
Motor and Sensory Neuropathy PanelSpecimen Type
VariesSpecimen Minimum Volume
1 mL
Specimen Stability Information
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Varies | Varies |
Reject Due To
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.Clinical Information
Hereditary motor and sensory neuropathy, or Charcot-Marie-Tooth (CMT) disease, is a major category of inherited peripheral neuropathies and is the most commonly inherited neuromuscular disorder. Individuals with CMT typically present with slowly progressive muscle weakness and atrophy primarily affecting the distal extremities.
Traditionally, the classification of CMT was based on nerve conduction velocity (NCV) and inheritance. The three neuropathy types based on NCV include demyelinating, axonal (non-demyelinating), and dominant intermediate CMT. Demyelinating CMT has a NCV less than 35 m/s and involves slowly progressive muscle weakness and atrophy and sensory loss. Often it can include pes cavus foot deformity and bilateral foot drop. Axonal CMT has a NCV greater than 45 m/s and includes distal muscle weakness and atrophy. Individuals tend to be less disabled and have less sensory loss than those with demyelinating neuropathy. Dominant-intermediate CMT has a NCV of 35 to 45 m/s and is consistent with a typical CMT phenotype.
Individuals with demyelinating polyneuropathy and an autosomal dominant family history of similar features can consider ordering testing for large deletions and duplications in the PMP22 gene (PMPDD / PMP22 Gene, Large Deletion/Duplication Analysis, Varies) as a first-tier test. Duplications in the PMP22 gene account for as much as 50% of all CMT.
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.
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 genes 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 genes 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. See Targeted Genes and Methodology Details for Inherited Motor and Sensory Neuropathy Gene Panel for details regarding the targeted genes analyzed for each test and specific gene regions not routinely covered.(Unpublished Mayo method)
Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.
Genes analyzed: AARS1, ABCD1, AIFM1, ARSA, ATP1A1, ATP7A, BAG3, BSCL2, C1orf194, CHCHD10, CNTNAP1, COX10, COX6A1, CTDP1, DGAT2, DHH, DNM2, DYNC1H1, EGR2, ERCC8, FAM126A, FBLN5, FGD4, FIG4, FMR1, GALC, GAN, GARS1, GBF1, GDAP1, GJB1, GLA, GNB4, HARS1, HINT1, HK1, HSPB1, HSPB8, IGHMBP2, INF2, KARS1, LAMA2, LITAF, LMNA, LRSAM1, MARS1, MCM3AP, MFN2, MORC2, MPV17, MPZ, MTMR2, NDRG1, NEFH, NEFL, PEX7, PHYH, PLEKHG5, PLP1, PMP2, PMP22, PNKP, POLG, PRPS1, PRX, RAB7A, SACS, SBF1, SBF2, SCO2, SH3TC2, SLC12A6, SLC25A46, SORD, SOX10, SURF1, TDP1, TFG, TRIM2, TRPV4, TSFM, TTR, TUBB3, TWNK, TYMP, VPS13D, and YARS1
Day(s) Performed
Varies
Performing Laboratory
Mayo Clinic Laboratories in RochesterTest 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
81448
LOINC Code Information
Test ID | Test Order Name | Order LOINC Value |
---|---|---|
IMSNP | Motor and Sensory Neuropathy Panel | 103728-2 |
Result ID | Test Result Name | Result LOINC Value |
---|---|---|
617585 | Test Description | 62364-5 |
617586 | Specimen | 31208-2 |
617587 | Source | 31208-2 |
617588 | Result Summary | 50397-9 |
617589 | Result | 82939-0 |
617590 | Interpretation | 69047-9 |
618181 | Additional Results | 82939-0 |
617591 | Resources | 99622-3 |
617592 | Additional Information | 48767-8 |
617593 | Method | 85069-3 |
617594 | Genes Analyzed | 48018-6 |
617595 | Disclaimer | 62364-5 |
617596 | Released By | 18771-6 |
Testing Algorithm
For more information see Hereditary Peripheral Neuropathy Diagnostic Algorithm