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Charcot-Marie-Tooth Autosomal Dominant Intermediate C via the YARS1/YARS 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
11817 YARS1 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11817YARS181479 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, and electromyography (EMG) and nerve conduction velocity (NCV) findings (Pareyson and Marchesi 2009; Bird 2015). CMT affects approximately 1 in 3,300 people.

Dominant intermediate Charcot-Marie-Tooth type is characterized by intermediate nerve conduction velocities and histological evidence of both axonal and demyelinating features. Individuals in the originally reported families exhibited a motor and sensory neuropathy with onset between age 10 and 60 years, distal leg weakness and atrophy, slow progression, and moderate severity (Jordanova et al. 2006). 

Genetics

Dominant intermediate Charcot-Marie-Tooth type C is inherited in an autosomal dominant manner due to pathogenic variants in YARS1/YARS, located on chromosome 1p35.1. The YARS1 gene encodes the tyrosyl-tRNA synthetase protein which is an enzyme responsible for catalyzing the aminoacylations of tRNATyr with tyrosine by a two-step mechansim. Thus far, pathogenic variants include missense, a small deletion, and a small indel in the YARS1 gene (Hyun et al. 2014; Jordanova et al. 2006; Gonzaga-Jauregui et al. 2015). 

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 YARS1 appear to be a rare cause of disease. Analytical sensitivity should be high because all reported pathogenic variants thus far are detectable by sequencing.

Thus far, no large deletions or duplications involving the YARS1 gene have been reported.

Testing Strategy

This test provides full coverage of all coding exons of the YARS1 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 an intermediate form of Charcot-Marie-Tooth Disease are candidates for testing. Testing is also indicated for family members of patients who have known YARS1 pathogenic variants.

Gene

Official Gene Symbol OMIM ID
YARS1 603623
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Charcot-Marie-Tooth Disease, Dominant Intermediate C AD 608323

Citations

  • Bird and Bird. 2015. PubMed ID: 20301532
  • Gonzaga-Jauregui C. et al. 2015. Cell Reports. 12: 1169-83. PubMed ID: 26257172
  • Hyun Y.S. et al. 2014. Clinical Genetics. 86: 592-4. PubMed ID: 24354524
  • Jordanova A. et al. 2006. Nature Genetics. 38: 197-202. PubMed ID: 16429158
  • Pareyson D., Marchesi C. 2009. The Lancet Neurology. 8: 65467. PubMed ID: 19539237

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

1) Select Test Method (Platform)


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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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