Charcot Marie Tooth - Axonal Neuropathy Sequencing Panel

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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NextGen Sequencing

Test Code Test Copy GenesCPT Code Copy CPT Codes
2645 AARS 81479 Add to Order
AIFM1 81479
COX6A1 81479
DHTKD1 81479
DNM2 81479
DYNC1H1 81479
FGD4 81479
FIG4 81406
GARS 81406
GDAP1 81405
GNB4 81479
HINT1 81479
HK1 81479
HSPB1 81404
HSPB8 81479
IGHMBP2 81479
INF2 81406
KARS 81479
KIF5A 81479
LMNA 81406
LRSAM1 81479
MARS 81479
MED25 81479
MFN2 81406
MPZ 81405
MTMR2 81479
NDRG1 81479
NEFL 81405
PDK3 81479
PLEKHG5 81479
PRPS1 81479
PRX 81405
RAB7A 81405
SBF1 81479
SBF2 81479
SH3TC2 81406
TRIM2 81479
TRPV4 81479
Full Panel Price* $640.00
Test Code Test Copy Genes Total Price CPT Codes Copy CPT Codes
2645 Genes x (38) $640.00 81404, 81405(x5), 81406(x6), 81479(x26) Add to Order
Pricing Comments

We are happy to accommodate requests for single genes or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered on our PGxome Custom Panel.

Targeted Testing

For ordering sequencing of targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 20 days.

Clinical Sensitivity

A genetic etiology can be identified in approximately 50-70% of individuals with CMT (Saporta et al. 2011; Rossor et al. 2013). Specifically, a molecular diagnosis can be identified in approximately 80-85% of individuals with demyelinating neuropathy (CMT1), and a molecular diagnosis can be identified in approximately 25-35% of individuals with axonal neuropathy (CMT2) (Bird 2015; Bird 2015; Rossor et al. 2013). The most common causative gene for CMT2 is MFN2 and accounts for about 10-20% of CMT2 cases (Bird 2015; Rossor 2013). The sensitivity of this panel will vary based on the clinical phenotype of the patient.

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Del/Dup via aCGH

Test Code Test Copy GenesPriceCPT Code Copy CPT Codes
600 AARS$990.00 81479 Add to Order
AIFM1$990.00 81479
COX6A1$990.00 81479
DHTKD1$990.00 81479
DNM2$990.00 81479
FGD4$990.00 81479
FIG4$990.00 81479
GARS$990.00 81479
GDAP1$990.00 81479
GNB4$990.00 81479
HINT1$990.00 81479
HK1$990.00 81479
HSPB1$990.00 81479
HSPB8$990.00 81479
IGHMBP2$990.00 81479
INF2$990.00 81479
KARS$990.00 81479
KIF5A$990.00 81479
LMNA$990.00 81479
LRSAM1$990.00 81479
MARS$990.00 81479
MED25$990.00 81479
MFN2$990.00 81479
MPZ$990.00 81479
MTMR2$990.00 81479
NDRG1$990.00 81479
NEFL$990.00 81479
PDK3$990.00 81479
PLEKHG5$990.00 81479
PRPS1$990.00 81479
PRX$990.00 81479
RAB7A$990.00 81479
SBF1$990.00 81479
SBF2$990.00 81479
SH3TC2$990.00 81479
TRIM2$990.00 81479
TRPV4$990.00 81479
Full Panel Price* $1490.00
Test Code Test Copy Genes Total Price CPT Codes Copy CPT Codes
600 Genes x (37) $1490.00 81479(x37) Add to Order
Pricing Comments

# of Genes Ordered

Total Price









Over 100

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Turnaround Time

The great majority of tests are completed within 20 days.

Clinical Sensitivity

The IGHMBP2, MPZ, MTMR2, SBF2, PRX, FIG4, and NDRG1 are genes in this panel with large copy number variants reported; however, clinical sensitivity has not been determined with a large cohort study (Human Gene Mutation Database).

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Clinical Features

Charcot Marie Tooth disease (CMT), also known as hereditary motor and sensory neuropathy (HMSN) is a large group of inherited disorders of the peripheral nerves. The progressive degeneration of motor nerves results in weakness and atrophy of the distal muscles. The degeneration of sensory nerves leads to decreased sensation, tingling and numbness in the legs, feet, arms and hands and neuropathic pain. The age of onset varies from childhood to mid adulthood. Symptoms usually begin with weakness and atrophy in the muscles of the legs and feet. As the disease progresses, weakness and atrophy of the muscles of the arms and hands may occur. CMT is heterogeneous in regards to symptoms, severity and progression rate. Although the disease may lead to disability and respiratory difficulty, life expectancy is usually unaffected. Most common symptoms include foot deformity, loss of balance, hammertoes, foot drop, frequent tripping and falls, and reduced manual dexterity (Bird 2015). Diagnosis is based on clinical features, family history, neurological examination, and electromyography (EMG) and nerve conduction velocity (NCV) findings (Rossor 2013; Bird 2015). CMT affects approximately 1 in 3,300 people (Bird 2015; Saporta 2011). Axonal forms of CMT primarily affect the axons of the peripheral nerves and are characterized by normal or near normal NCV and reduced amplitudes. Demyelinating forms of CMT primarily affect the myelin sheath of the peripheral nerve and are characterized by slow nerve conduction velocities (NCV) of less than 38 m/s in upper limbs. Intermediate NCV of 25-45 m/s can be difficult to classify as axonal or demyelinating. This panel includes genes that cause a strict CMT2 (axonal) phenotype, in addition to genes that cause intermediate forms with axonal and/or demyelinating conductions.


Charcot-Marie-Tooth can be inherited in an autosomal dominant, autosomal recessive or an X-linked manner. The MPZ, NEFL, MFN2, RAB7, TRPV4, GARS, HSPB1, HSPB8, INF2, GNB4, AARS, DYNC1H1, LRSAM1, DHTKD1, MARS, and KIF5A genes are involved in autosomal dominant CMT. Autosomal recessive forms of CMT involve the LMNA, MED25, HINT1, TRIM2, MTMR2, SBF2, SBF1, SH3TC2, PRX, FGD4, FIG4, NDRG1, HK1, KARS, PLEKHG5, IGHMBP2 and COX6A1 genes. Pathogenic variants in the EGR2, GDAP1, and DNM2 genes can exhibit both dominant and recessive inheritance. In cases of Dejerine-Sottas syndrome, the MPZ and PRX genes can exhibit both dominant and recessive inheritance as well. Pathogenic variants in the AIFM1, PRPS1, and PDK3 genes are inherited in an X-linked manner. See individual gene test descriptions for information on molecular biology of gene products.

Testing Strategy

For this NextGen panel, the full coding regions plus ~10 bp of non-coding DNA flanking each exon are sequenced for each of the genes listed below. Sequencing is accomplished by capturing specific regions with an optimized solution-based hybridization kit, followed by massively parallel sequencing of the captured DNA fragments. Additional Sanger sequencing is performed for any regions not captured or with insufficient number of sequence reads. All pathogenic, likely pathogenic, or variants of uncertain significance are confirmed by Sanger sequencing. Please note that for technical reasons, exon 8 of the INF2 gene is not currently included this panel. Thus far, only exons 2 to 6, especially exons 2 to 4 that encode the diaphanous inhibitory domain (DID), have been reported to harbor pathogenic INF2 variants (Boyer et al. 2011; Barua et al. 2013; Human Gene Mutation Database).

Indications for Test

Individuals with clinical symptoms consistent with an axonal neuropathy (near normal nerve conduction velocities with decreased amplitudes).


Name Inheritance OMIM ID
Charcot-Marie-Tooth Disease Dominant Intermediate 3 AD 607791
Charcot-Marie-Tooth Disease Type 2B AR 600882
Charcot-Marie-Tooth Disease Type 2B1 AR 605588
Charcot-Marie-Tooth Disease Type 2B2 AR 605589
Charcot-Marie-Tooth Disease Type 2C AR 606071
Charcot-Marie-Tooth Disease Type 2D AR 601472
Charcot-Marie-Tooth Disease Type 2E AR 607684
Charcot-Marie-Tooth Disease Type 2F AR 606595
Charcot-Marie-Tooth Disease Type 2I AR 607677
Charcot-Marie-Tooth Disease Type 2J AR 607736
Charcot-Marie-Tooth Disease Type 2K AR 607831
Charcot-Marie-Tooth Disease, Axonal, Type 2O AR 614228
Charcot-Marie-Tooth Disease, Axonal, With Vocal Cord Paresis, Autosomal Recessive AR 607706
Charcot-Marie-Tooth Disease, Dominant Intermediate B AD 606482
Charcot-Marie-Tooth Disease, Dominant Intermediate E AD 614455
Charcot-Marie-Tooth Disease, Dominant Intermediate F AD 615185
Charcot-Marie-Tooth Disease, Recessive Intermediate A AR 608340
Charcot-Marie-Tooth Disease, Recessive Intermediate B AR 613641
Charcot-Marie-Tooth Disease, Recessive Intermediate C AR 615376
Charcot-Marie-Tooth Disease, Recessive Intermediate D AR 616039
Charcot-Marie-Tooth Disease, Type 1F AD,AR 607734
Charcot-Marie-Tooth Disease, Type 2A2 AR 609260
Charcot-Marie-Tooth Disease, Type 2L AR 608673
Charcot-Marie-Tooth Disease, Type 2N AR 613287
Charcot-Marie-Tooth Disease, Type 2Q AD 615025
Charcot-Marie-Tooth Disease, Type 2R XL 615490
Charcot-Marie-Tooth Disease, Type 2S AR 616155
Charcot-Marie-Tooth Disease, Type 2U AD 616280
Charcot-Marie-Tooth Disease, Type 3 AR 145900
Charcot-Marie-Tooth Disease, Type 4A AR 214400
Charcot-Marie-Tooth Disease, Type 4B1 AR 601382
Charcot-Marie-Tooth Disease, Type 4B2 AR 604563
Charcot-Marie-Tooth Disease, Type 4B3 AR 615284
Charcot-Marie-Tooth Disease, Type 4C AR 601596
Charcot-Marie-Tooth Disease, Type 4D AR 601455
Charcot-Marie-Tooth Disease, Type 4E AR 605253
Charcot-Marie-Tooth Disease, Type 4F AR 614895
Charcot-Marie-Tooth Disease, Type 4H AR 609311
Charcot-Marie-Tooth Disease, Type 4J AR 611228
Charcot-Marie-Tooth Disease, Type Ib AD 118200
Charcot-Marie-Tooth Disease, X-linked Dominant, 6 AR 300905
Charcot-Marie-Tooth Disease, X-Linked Recessive, Type 5 XL 311070
Charcot-Marie-Toothe Disease, Type 2P AD,AR 614436
Neuropathy, Hereditary Motor and Sensory, Russe Type AR 605285
Neuropathy, Hereditary Motor and Sensory, Type VIA AD 601152

Related Tests

AIFM1-Related Disorders via AIFM1 Gene Sequencing with CNV Detection
KARS-Related Disorders via the KARS Gene
MFN2-Related Disorders via the MFN2 Gene
TRPV4-related Disorders via the TRPV4 Gene
Autism Spectrum Disorders and Intellectual Disability (ASD-ID) Comprehensive Sequencing Panel with CNV Detection
Charcot Marie Tooth Disease via COX6A1 Gene Sequencing with CNV Detection
Charcot Marie Tooth Type 2U via the MARS Gene
Charcot Marie Tooth Type 4J via the FIG4 Gene
Charcot-Marie-Tooth Autosomal Dominant Intermediate F via the GNB4 Gene
Charcot-Marie-Tooth disease, axonal, type 20, Spinal muscular atrophy with lower extremity predominance and Mental retardation, autosomal dominant type 13 via the DYNC1H1 Gene
Charcot-Marie-Tooth Type 2E/1F via NEFL Gene Sequencing with CNV Detection
Charcot-Marie-Tooth Type 4B1 via the MTMR2 Gene
Charcot-Marie-Tooth Type 4B2 via the SBF2 Gene
Charcot-Marie-Tooth Type 4B3 via the SBF1 Gene
Charcot-Marie-Tooth Type 4D via NDRG1 Gene Sequencing with CNV Detection
Comprehensive Cardiology Sequencing Panel with CNV Detection
Comprehensive Neuromuscular Sequencing Panel
Congenital Muscular Dystrophy Sequencing Panel
Congenital Myopathy Sequencing Panel
Dilated Cardiomyopathy Sequencing Panel with CNV Detection
Dynamin-2 Related Disorders via the DNM2 Gene
Glycyl tRNA Synthetase-Related Disorders via the GARS Gene
Heat Shock 22 kDa Protein-Related Disorders via the HSPB8 Gene
Heat Shock 27 kDa Protein-Related Disorders via the HSPB1 Gene
Hereditary Motor and Sensory Neuropathy IIB (HMSN2B) via RAB7A Gene Sequencing with CNV Detection
Hutchinson-Gilford Progeria Syndrome (HGPS) via the LMNA Gene
Laminopathies via the LMNA Gene
Left Ventricular Noncompaction (LVNC) Sequencing Panel with CNV Detection
Limb-Girdle Muscular Dystrophy (LGMD) Sequencing Panel
MPZ-Related Neuropathies via MPZ Gene Sequencing with CNV Detection
Pan Cardiomyopathy Sequencing Panel with CNV Detection
Peripheral Neuropathies via the HINT1 Gene
Spastic Paraplegia 10 via KIF5A Gene Sequencing with CNV Detection
Spinal Muscular Atrophy with Respiratory Distress Type 1 via the IGHMBP2 Gene
Sudden Cardiac Arrest Sequencing Panel with CNV Detection


Genetic Counselors
  • Barua M. et al. 2013. Kidney International. 83: 316-22. PubMed ID: 23014460
  • Bird T.D. 2015. Charcot-Marie-Tooth Hereditary Neuropathy Overview. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301532
  • Bird T.D. 2015. Charcot-Marie-Tooth Neuropathy Type 1. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301384
  • Boyer O. et al. 2011. Journal of the American Society of Nephrology : Jasn. 22: 239-45. PubMed ID: 21258034
  • Human Gene Mutation Database (Bio-base).
  • Rossor A.M. et al. 2013. Nature Reviews. Neurology. 9: 562-71. PubMed ID: 24018473
  • Saporta A.S. et al. 2011. Annals of Neurology. 69: 22-33. PubMed ID: 21280073
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NextGen Sequencing using PG-Select Capture Probes

Test Procedure

We use a combination of Next Generation Sequencing (NGS) and Sanger sequencing technologies to cover the full coding regions of the listed genes plus ~10 bases of non-coding DNA flanking each exon.  As required, genomic DNA is extracted from the patient specimen.  For NGS, patient DNA corresponding to these regions is captured using an optimized set of DNA hybridization probes.  Captured DNA is sequenced using Illumina’s Reversible Dye Terminator (RDT) platform (Illumina, San Diego, CA, USA).  Regions with insufficient coverage by NGS are often covered by Sanger sequencing.

For Sanger sequencing, Polymerase Chain Reaction (PCR) is used to amplify targeted regions.  After purification of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  PCR products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In nearly all cases, cycle sequencing is performed separately in both the forward and reverse directions.

Patient DNA sequence is aligned to the genomic reference sequence for the indicated gene region(s). All differences from the reference sequences (sequence variants) are assigned to one of five interpretation categories, listed below, per ACMG Guidelines (Richards et al. 2015).

(1) Pathogenic Variants
(2) Likely Pathogenic Variants
(3) Variants of Uncertain Significance
(4) Likely Benign Variants
(5) Benign Variants

Human Genome Variation Society (HGVS) recommendations are used to describe sequence variants (  Rare variants and undocumented variants are nearly always classified as likely benign if there is no indication that they alter protein sequence or disrupt splicing.

Analytical Validity

As of March 2016, 6.36 Mb of sequence (83 genes, 1557 exons) generated in our lab was compared between Sanger and NextGen methodologies. We detected no differences between the two methods. The comparison involved 6400 total sequence variants (differences from the reference sequences). Of these, 6144 were nucleotide substitutions and 256 were insertions or deletions. About 65% of the variants were heterozygous and 35% homozygous. The insertions and deletions ranged in length from 1 to over 100 nucleotides.

In silico validation of insertions and deletions in 20 replicates of 5 genes was also performed. The validation included insertions and deletions of lengths between 1 and 100 nucleotides. Insertions tested in silico: 2200 between 1 and 5 nucleotides, 625 between 6 and 10 nucleotides, 29 between 11 and 20 nucleotides, 25 between 21 and 49 nucleotides, and 23 at or greater than 50 nucleotides, with the largest at 98 nucleotides. All insertions were detected. Deletions tested in silico: 1813 between 1 and 5 nucleotides, 97 between 6 and 10 nucleotides, 32 between 11 and 20 nucleotides, 20 between 21 and 49 nucleotides, and 39 at or greater than 50 nucleotides, with the largest at 96 nucleotides. All deletions less than 50 nucleotides in length were detected, 13 greater than 50 nucleotides in length were missed. Our standard NextGen sequence variant calling algorithms are generally not capable of detecting insertions (duplications) or heterozygous deletions greater than 100 nucleotides. Large homozygous deletions appear to be detectable.   

Analytical Limitations

Interpretation of the test results is limited by the information that is currently available.  Better interpretation should be possible in the future as more data and knowledge about human genetics and this specific disorder are accumulated.

When Sanger sequencing does not reveal any difference from the reference sequence, or when a sequence variant is homozygous, we cannot be certain that we were able to detect both patient alleles.  Occasionally, a patient may carry an allele which does not amplify, due to a large deletion or insertion.   In these cases, the report will contain no information about the second allele.  Our Sanger and NGS Sequencing tests are generally not capable of detecting Copy Number Variants (CNVs).

We sequence all coding exons for each given transcript, plus ~10 bp of flanking non-coding DNA for each exon.  Test reports contain no information about other portions of the gene, such as regulatory domains, deep intronic regions or any currently uncharacterized alternative exons.

In most cases, we are unable to determine the phase of sequence variants.  In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants due to somatic mosaicism is limited.  Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR.

Unless otherwise indicated, DNA sequence data is obtained from a specific cell-type (usually leukocytes from whole blood).   Test reports contain no information about the DNA sequence in other cell-types.

We cannot be certain that the reference sequences are correct.

Rare, low probability interpretations of sequencing results, such as for example the occurrence of de novo mutations in recessive disorders, are generally not included in the reports.

We have confidence in our ability to track a specimen once it has been received by PreventionGenetics.  However, we take no responsibility for any specimen labeling errors that occur before the sample arrives at PreventionGenetics.

Deletion/Duplication Testing via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

Order Kits

Ordering Options

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.
  • 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.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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