CANDLE Syndrome via the PSMB8 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
8629 PSMB8 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8629PSMB881479 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

Clinical Features and Genetics

Clinical Features

Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated Temperature (CANDLE) syndrome is a rare autoinflammatory disease due to impairment of proteasome function. Symptom onset occurs within the first two weeks to 6 months of life with recurrent fevers, violaceous cutaneous plaques covering trunk and extremities, swollen eyelids, thick lips, and facial lipodystrophy. Patients also can present with conjunctivitis, delayed physical development, joint pain without arthritis, chondrites of the ear and nose, myositis, hepatosplenomegaly, microcytic anemia, and muscle atrophy. In severe cases, inflammatory attacks can result in organ failure and sudden death. Genetic testing is helpful in the differential diagnosis of CANDLE from other autoinflammatory syndromes including cryopyrin-associated periodic syndromes (CAPS), Majeed syndrome, and Hyper IgD syndrome (Sanchez et al. 2013; Arima et al. 2011; Kluk et al. 2014; Agarwal et al. 2010; Liu et al. 2012).

Genetics

CANDLE syndrome is inherited in an autosomal recessive manner through pathogenic variants in the PSMB8 gene. Missense variants, found throughout the protein, have been reported in all but one case. The exception was a patient homozygous for a nonsense variant (Sanchez et al. 2013; Arima et al. 2011; Kluk et al. 2014; Agarwal et al. 2010; Liu et al 2012). The PSMB8 gene encodes the β5i proteasome subunit which is involved in degrading ubiquitin tagged proteins. Missense variants in the PSMB8 gene result in incorporation of other proteasome subunits to the complex resulting in heightened inflammatory signaling (Arima et al. 2011).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity cannot be estimated because only a small number of cases have been reported to date. Analytical sensitivity should be high as all pathogenic variants reported to date are detectable by sequencing.

No large deletions or duplications involving PSMB8 have been reported (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the PSMB8 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 testing present with elevated c-reactive protein, erythrocyte sedimentation rates, IL-6, IP-10, MCP-1 and hepatic transaminase levels. Initial symptoms include recurrent fevers and cutaneous plaques within the first few months of life (Sanchez et al. 2013). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in PSMB8.

Gene

Official Gene Symbol OMIM ID
PSMB8 177046
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
Periodic Fever Syndromes Panel

Citations

  • Agarwal A.K. et al. 2010. American Journal of Human Genetics. 87: 866-72. PubMed ID: 21129723
  • Arima K. et al. 2011. Proceedings of the National Academy of Sciences of the United States of America. 108: 14914-9. PubMed ID: 21852578
  • Human Gene Mutation Database (Bio-base).
  • Kluk J. et al. 2014. The British Journal of Dermatology. 170: 215-7. PubMed ID: 24001180
  • Liu Y. et al. 2012. Arthritis and Rheumatism. 64: 895-907. PubMed ID: 21953331
  • Sanchez G.A. et al. 2013. Rheumatic Diseases Clinics of North America. 39: 701-34. PubMed ID: 24182851

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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