Papillon-Lefevre Syndrome (PLS) via the CTSC 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
8403 CTSC 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8403CTSC81479 81479(x2) $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

  • Siwu Peng, PhD

Clinical Features and Genetics

Clinical Features

Papillon-Lefevre syndrome (PLS, OMIM 245000) is characterized by palmoplantar hyperkeratosis (thickening of skin on palms and souls of feet) and severe early onset periodontitis resulting in the premature loss of primary and secondary teeth (Gorlin et al. J Pediatr 65:895-908, 1964; Haneke Hum Genet 51:1-35, 1979). Palmoplantar keratosis usually develops in PLS patients by 3 years of age and varies from mild scaly skin to overt hyperkeratosis. Clinically, it is the periodontitis that distinguishes PLS from other forms of palmoplantar keratosis. The periodontitis of PLS is generally very aggressive and unresponsive to therapies, though in some very rare cases periodontitis is mild or late onset (Fardal et al. J Clin Periodontol 25:181-184, 1998). Consequently, most PLS patients lose all of their teeth by 20 years of age. PLS is ascertained mainly by dentists because of the severe periodontitis. Teeth are affected in the order of eruption and accompanied by inflamed periodontal tissue, bleeding of gums, pocket formation, and loosening with no sign of root resorption. In addition, some PLS patients may be more susceptible to infections because of an aberrant immune response (Haneke Hum Genet 51:1-35, 1979).

Genetics

PLS exhibits an autosomal recessive pattern of inheritance and is caused by variants in the CTSC gene (Hart et al. J Med Genet 36:881-887, 1999; Toomes et al. Nat Genet 23:421-424, 1999). The frequency of PLS is approximately 1-4 per million people (Gorlin et al. J Pediatr 65:895-908, 1964). CTSC encodes cathepsin C (CTSC), a lysosomal protease and endopeptidase. CTSC is expressed in tissues involved in the immune response, e.g. bone marrow-derived myeloid and lymphoid cells, and plays an essential role in protein degradation and pro-enzyme activation including activation of granule serine proteases involved in a variety of immune responses (McGuire J Biol Chem 268:2458-2467, 1993; Rao et al. J Biol Chem 272:10260-10265, 1997). Consequently, loss of functional CTSC may be linked to an attenuated host response against bacteria in dental plaque and susceptibility to periodontitis (see Toomes et al. Nat Genet 23:421-424, 1999, for discussion). Causative variants in the CTSC gene include numerous missense and nonsense variants and to a lesser extent splicing variants, insertions, and deletions. No predominant variants have been reported, and no obvious genotype-phenotype correlation exists.

Clinical Sensitivity - Sequencing with CNV PGxome

No variants in genes other than CTSC have been reported to cause PLS.

Testing Strategy

This test provides full coverage of all coding exons of the CTSC 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 periodontitis, palmoplantar keratosis, and anyone with a family history of PLS or severe and rapid tooth loss. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CTSC.

Gene

Official Gene Symbol OMIM ID
CTSC 602365
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Papillon-Lefevre Syndrome AR 245000

Citations

  • Fardal, O., et.al. (1998). "Palmar plantar keratosis and unusual periodontal findings. Observations from a family of 4 members." J Clin Periodontol 25(2): 181-4. PubMed ID: 9495618
  • Gorlin, R. J., et.al. (1964). "The Syndrome of Palmar-Plantar Hyperkeratosis and Premature Periodontal Destruction of the Teeth. a Clinical and Genetic Analysis of the Papillon-Lef PubMed ID: 14244097
  • Haneke, E. (1979). "The Papillon-Lefevre syndrome: keratosis palmoplantaris with periodontopathy. Report of a case and review of the cases in the literature." Hum Genet 51(1): 1-35. PubMed ID: 159254
  • Hart, T. C., et.al. (1999). "Mutations of the cathepsin C gene are responsible for Papillon-Lefevre syndrome." J Med Genet 36(12): 881-7. PubMed ID: 10593994
  • McGuire, M. J., et.al. (1993). "Generation of active myeloid and lymphoid granule serine proteases requires processing by the granule thiol protease dipeptidyl peptidase I." J Biol Chem 268(4): 2458-67. PubMed ID: 8428921
  • Toomes, C., et.al. (1999). "Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis." Nat Genet 23(4): 421-4. PubMed ID: 10581027

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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