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Charcot-Marie-Tooth Type X-linked Dominant 6 via the PDK3 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
11565 PDK3 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11565PDK381479 81479,81479 $990 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 platform).

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

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

For Sanger Sequencing click here.

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), nerve conduction velocity (NCV), and genetic testing (Pareyson and Marchesi, 2009. PubMed ID: 19539237; Bird, 2015. PubMed ID: 20301532). CMT affects approximately 1 in 3,300 people.

Charcot-Marie-Tooth X-linked Dominant 6 (CMTX6) was first described in a large 3 generation family in which linkage analysis and whole exome sequencing were used to discover the causative PDK3 gene (Kennerson et al., 2013). An additional unrelated family with a similar presentation was later described (Kennerson et al., 2016). Affected males had a more severe and earlier onset than carrier females. Typical symptoms included foot deformities, abnormal gait due to distal lower limb muscle weakness and atrophy, sensory abnormalities, and decreased hand grip strength and dexterity. Female carriers did not show symptoms until much later and were mild in comparison, such as hand muscle weakness, hand tremor, and decreased ankle reflexes. The predominant EMG finding was an axonal motor and sensory polyneuropathy with variable mild conduction slowing.

Genetics

Charcot-Marie-Tooth X-linked Dominant 6 (CMTX6) is inherited in an X-linked manner due to pathogenic variants in PDK3, located on chromosome Xp22.11. The PDK3 gene encodes pyruvate dehydrogenase kinase isoenzyme 3 (PDK3), one of four PDK isoenzymes, which negatively regulates the activity of the pyruvate dehydrogenase complex by reverse phosphorylation. Thus far, the only established pathogenic variant reported in two unrelated families is a missense variant referred to as c.473G>A p.Arg158His, which results in hyperactivity and gain-of-function (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 PDK3 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 PDK3 gene have been reported (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the PDK3 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 X-lniked inheritance. Testing is also indicated for family members of patients who have known PDK3 pathogenic variants.

Gene

Official Gene Symbol OMIM ID
PDK3 300906
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Charcot-Marie-Tooth Disease, X-linked Dominant, 6 XL 300905

Citations

  • Bird, 2015. PubMed ID: 20301532
  • Human Gene Mutation Database (Bio-base).
  • Kennerson et al., 2013. PubMed ID: 23297365
  • Kennerson et al., 2016. PubMed ID: 26801680
  • Pareyson and Marchesi, 2009. 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)


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.
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