Charcot-Marie-Tooth (CMT) - Axonal Neuropathy Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10409 AARS1 81479,81479 Order Options and Pricing
AIFM1 81479,81479
COX6A1 81479,81479
DHTKD1 81479,81479
DNM2 81479,81479
DYNC1H1 81479,81479
FGD4 81479,81479
FIG4 81406,81479
GARS1 81406,81479
GDAP1 81405,81479
GNB4 81479,81479
HINT1 81479,81479
HSPB1 81404,81479
HSPB8 81479,81479
IGHMBP2 81479,81479
INF2 81406,81479
KARS1 81479,81479
KIF5A 81479,81479
LMNA 81406,81479
LRSAM1 81479,81479
MARS1 81479,81479
MED25 81479,81479
MFN2 81406,81479
MPZ 81405,81479
MTMR2 81479,81479
NDRG1 81479,81479
NEFL 81405,81479
PDK3 81479,81479
PLEKHG5 81479,81479
PRPS1 81479,81479
PRX 81405,81479
RAB7A 81405,81479
SBF1 81479,81479
SBF2 81479,81479
SH3TC2 81406,81479
TRIM2 81479,81479
TRPV4 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10409Genes x (37)81479 81404, 81405, 81406, 81479 $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel 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 via our PGxome Custom Panel tool.

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

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

Clinical Features and Genetics

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.

Genetics

Charcot-Marie-Tooth can be inherited in an autosomal dominant, autosomal recessive or an X-linked manner. The MPZ, NEFL, MFN2, RAB7, TRPV4, GARS1/GARS, HSPB1, HSPB8, INF2, GNB4, AARS1/AARS, DYNC1H1, LRSAM1, DHTKD1, MARS1/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, KARS1/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.

Clinical Sensitivity - Sequencing with CNV PGxome

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.

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).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 99.9% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or 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).

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

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

Diseases

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, Type VIA AD 601152

Related Test

Name
PGxome®

Citations

  • Barua M. et al. 2013. Kidney International. 83: 316-22. PubMed ID: 23014460
  • Bird and Bird. 2015. 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 et al. 2013. PubMed ID: 24018473
  • Saporta et al. 2011. PubMed ID: 21280073

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.

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


Specimen Types

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