Charcot-Marie-Tooth 1C via the LITAF Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesPrice Test CPT CodeGene CPT Codes Copy CPT Codes STAT
9077 LITAF$890 8140481404,81479 Add to Order

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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

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

For Sanger Sequencing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

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.

Charcot-Marie-Tooth type 1C (CMT1C) is a demyelinating form of CMT that primarily affects the myelin sheath of the peripheral nerve. Patients with CMT1C will exhibit the typical slow nerve conduction velocities (NCV) of a demyelinating neuropathy, distal muscle weakness and atrophy, depressed deep tendon reflexes, and sensory impairment. Onset is typically in the 30-50s, but early onset in the first decade has also been reported (Ciotti et al. 2014).

Genetics

Charcot-Marie-Tooth type 1C (CMT1C) is inherited in an autosomal dominant manner due to pathogenic variants in LITAF, located on chromosome 16p13.13. The LITAF gene encodes the lipopolysaccharide-induced TNF-α factor (LITAF) protein which is involved in cytokine signaling and tumor suppression; however, the exact cellular role is not fully understood. Thus far, all reported pathogenic variants have been missense variants (Human Gene Mutation Database; Ciotti et al. 2014; Street et al. 2003).

Testing Strategy

This test provides full coverage of all coding exons of the LITAF 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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Clinical Sensitivity - Sequencing with CNV

A genetic etiology can be identified in approximately 50-70% of individuals with Charcot-Marie-Tooth (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). CMT1A (70%-80% of all CMT1) involves duplication of the PMP22 gene. CMT1B (6%-10% of all CMT1) is associated with single-nucleotide variants in MPZ (Bird 2015). CMT1C (1%-2% of all CMT1) is associated with pathogenic variants in LITAF, and CMT1D (<2% of all CMT1) is associated with pathogenic variants in EGR2.

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

Indications for Test

Individuals with clinical symptoms consistent with Charcot-Marie-Tooth Type 1 are candidates for testing. Testing is also indicated for family members of patients who have known LITAF pathogenic variants.

Gene

Official Gene Symbol OMIM ID
LITAF 603795
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Charcot-Marie-Tooth Disease, Type IC AD 601098

Related Tests

Name
Charcot-Marie-Tooth - Comprehensive Panel
Charcot-Marie-Tooth - Demyelinating Neuropathy Panel

Citations

  • 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
  • Ciotti P. et al. 2014. Journal of the Neurological Sciences. 343: 183-6. PubMed ID: 24880540
  • Human Gene Mutation Database (Bio-base).
  • Pareyson D., Marchesi C. 2009. The Lancet Neurology. 8: 654–67. PubMed ID: 19539237
  • Rossor A.M. et al. 2013. Nature Reviews Neurology. 9: 562-571. PubMed ID: 24018473
  • Saporta et al. 2011. PubMed ID: 21280073
  • Street V.A. et al. 2003. Neurology. 60: 22-6. PubMed ID: 12525712

Ordering/Specimens

Ordering Options

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.

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

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