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Charcot-Marie-Tooth Disease via the COX6A1 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
9075 COX6A1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9075COX6A181479 81479,81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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 backbone).

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

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days 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. 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 (Pareyson and Chiara 2009). CMT affects approximately 1 in 3,300 people (Bird 2015).

Tamiya et al. (2014) reported 3 patients from 2 unrelated consanguineous Japanese families with early-onset peripheral neuropathy due to a homozygous COX6A1 pathogenic variant. Affected individuals showed distal muscle weakness and atrophy, pes cavus, steppage gait, clawing of the toes, distal sensory impairment, and areflexia of the lower limbs. Disease progression was slow over 2 decades in all individuals. Affected members of one family had onion bulb formation in the sural nerve biopsy. The female proband in the second family had mildly slowed NCV consistent with an axonal neuropathy, but a sural nerve biopsy was not performed (Tamiya et al. 2014). NCV values ranged from 35.7 m/s to 49.6 m/s depending on patient age and nerve studied. COX6A1 therefore causes an intermediate form of CMT. In an additional report, a separate group reported similar clinical features in a 37 year old patient that was homozygous for the same pathogenic COX6A1 variant seen in the the previously reported individuals (Lassuthova et al. 2015).

Genetics

Charcot-Marie-Tooth, Intermediate type D is inherited in an autosomal recessive manner due to pathogenic variants in COX6A1, located on chromosome 12q24.2 (Tamiya et al. 2014). The COX6A1 gene encodes the cytochrome oxidase subunit VIa polypeptide I which is required for stability of the cytochrome c oxidase holoenzyme. A small intronic deletion near the consensus acceptor splice site (c.247-7_c.247-3del) is the only reported pathogenic variant so far. Haplotype analysis suggests this variant arose independently in the reported three affected families and is a mutational hotspot (Lassuthova et al. 2015; Tamiya et al. 2014).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity cannot be estimated because only a small number of patients have been reported. Analytical sensitivity may be high because the only reported pathogenic variant thus far is detectable by sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the COX6A1 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

Candidates for this test are patients with a suspected intermediate form of Charcot-Marie-Tooth disease. Testing is also indicated for family members of patients who have known pathogenic variants in the COX6A1 gene. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in COX6A1.

Gene

Official Gene Symbol OMIM ID
COX6A1 602072
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Name
Charcot-Marie-Tooth (CMT) - Axonal Neuropathy Panel
Charcot-Marie-Tooth (CMT) - Comprehensive Panel
Charcot-Marie-Tooth (CMT) - Demyelinating Neuropathy Panel

Citations

  • Bird and Bird. 2015. PubMed ID: 20301532
  • Laššuthová P et al. 2015. Clinical Genetics. N/A: N/A. PubMed ID: 26302975
  • Pareyson D., Marchesi C. 2009. The Lancet Neurology. 8: 654–67. PubMed ID: 19539237
  • Tamiya G et al. 2014. The American Journal of Human Genetics. 95: 294-300. PubMed ID: 25152455

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


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


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.
Total Price: $
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