Charcot-Marie-Tooth (CMT) - Comprehensive Panel
Summary and Pricing
Test MethodExome Sequencing with CNV Detection
|Test Code||Test Copy Genes||Gene CPT Codes Copy CPT Codes|
|10419||AARS1||81479,81479||Order Options and Pricing|
|Test Code||Test Copy Genes||Panel CPT Code||Gene CPT Codes Copy CPT Code||Base Price|
|10419||Genes x (44)||81479||81324, 81325, 81403, 81404, 81405, 81406, 81479||$890||Order Options and Pricing|
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.
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.
For ordering sequencing of targeted known variants, go to our Targeted Variants page.
Clinical Features and Genetics
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).
This comprehensive panel includes genes that are causative for the different types of CMT. 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. Axonal forms of CMT primarily affect the axons of the peripheral nerves and are characterized by normal or almost normal NCV of greater than 38 m/s. Intermediate NCV of 25-45 m/s can be difficult to classify as axonal or demyelinating.
Approximately 70% of CMT1 is caused by the recurrent PMP22 duplication (Bird 2015; Li et al. 2013; van Paassen et al. 2014). CMT1A is most commonly caused by a 1.5 Mb duplication of chromosome 17p11.2 which includes the PMP22 gene. PMP22 deletion/duplication testing via aCGH can be ordered through test code #600.
Charcot-Marie-Tooth can be inherited in an autosomal dominant, autosomal recessive or an X-linked manner. The MPZ, LITAF, NEFL, PMP22, FBLN5, MFN2, YARS1/YARS, RAB7, TRPV4, GARS1/GARS, HSPB1, HSPB8, INF2, GNB4, AARS1/AARS, DYNC1H1, LRSAM1, DHTKD1, MARS1/MARS, 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, CTDP1, 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 PMP22, MPZ, EGR2, and PRX genes can exhibit both dominant and recessive inheritance as well. Pathogenic variants in the GJB1, 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 sensitivity of this panel will vary based on the clinical phenotype of the patient.
It is estimated that ~70% of all Charcot Marie Tooth Type 1 (CMT1) is due to the PMP22 1.5 Mb duplication, while only around 5% of CMT1 cases are due to point mutations (Bird 2015). The IGHMBP2, MPZ, EGR2, MTMR2, SPF2, PRX, FIG4, NDRG1 are other 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).
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 in 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
Any patient with clinical symptoms consistent with a peripheral neuropathy.
Any patient with clinical symptoms consistent with a peripheral neuropathy.
- 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).
- Li et al. 2013. PubMed ID: 23224996
- Rossor et al. 2013. PubMed ID: 24018473
- Saporta et al. 2011. PubMed ID: 21280073
- van Paassen B.W. et al. 2014. Orphanet Journal of Rare Diseases. 9: 38. PubMed ID: 24646194
- Zhang F. et al. 2010. American Journal of Human Genetics. 86: 892-903. PubMed ID: 20493460
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.
- 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.