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Charcot-Marie-Tooth Type 2R via the TRIM2 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
TRIM2 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11767TRIM281479 81479,81479 $990 Order Options and Pricing

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

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn 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

  • Angela Gruber, PhD

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; and 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 muscle 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. Diagnosis is based on clinical features, family history, neurological examination, electromyography (EMG), and nerve conduction velocity (NCV) findings (Pareyson and Marchesi. 2009. PubMed ID: 19539237; Bird. 2015. PubMed ID: 20301532). CMT affects approximately 1 in 3,300 people.

Charcot-Marie-Tooth type 2R (CMT2R) is an autosomal recessive form of CMT that presents in infancy or early childhood. Two unrelated patients have been reported thus far with pathogenic variants in the TRIM2 gene. The first reported patient had an early-onset axonal neuropathy that presented with mild delay of motor development, hypotonia, atrophy of small muscles in the hands and feet, pes cavus, and a sural nerve biopsy with nonspecific axonal degeneration (Ylikallio et al. 2013. PubMed ID: 23562820). The second patient had a more severe phenotype with respiratory insufficiency associated with vocal cord paralysis, axial hypotonia, muscle weakness, knee contractures, pes equinus, pes cavus, and absent deep tendon reflexes. The EMG was consistent with a severe axonal polyneuropathy (Pehlivan et al. 2015. PubMed ID: 25893792).

Genetics

Charcot-Marie-Tooth type 2R is inherited in an autosomal recessive manner due to pathogenic variants in TRIM2, located on chromosome 4q31.13. The TRIM2 gene encodes tripartite-motif containing protein 2 which functions as an E3 ubiquitin ligase. TRIM2 is a highly expressed protein in the nervous system that binds and regulates ubiquination of the neurofilament light subunit protein (Balastik et al. 2008. PubMed ID: 18687884). Thus far, reported pathogenic variants include missense variants and a small deletion that results in a frameshift and premature protein termination (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity cannot be estimated because only a small number of patients have been reported. However, pathogenic variants in TRIM2 appear to be a rare cause of disease. Analytical sensitivity should be high because almost all reported pathogenic variants thus far are detectable by sequencing.

Thus far, no large deletions or duplications involving the TRIM2 gene have been reported (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the TRIM2 gene 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 full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Individuals with clinical symptoms consistent with Charcot-Marie-Tooth and autosomal recessive inheritance. Testing is also indicated for family members of patients who have known TRIM2 pathogenic variants. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in TRIM2.

Gene

Official Gene Symbol OMIM ID
TRIM2 614141
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Charcot-Marie-Tooth Disease, Type 2R AR 615490

Citations

  • Balastik et al. 2008. PubMed ID: 18687884
  • Bird. 2015. PubMed ID: 20301532
  • Human Gene Mutation Database (Bio-base).
  • Pareyson and Marchesi. 2009. PubMed ID: 19539237
  • Pehlivan et al. 2015. PubMed ID: 25893792
  • Ylikallio et al. 2013. PubMed ID: 23562820

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.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

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

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

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View Ordering Instructions

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2) Select Additional Test Options

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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