Familial Cold Autoinflammatory Syndrome 2 via the NLRP12 Gene
Summary and Pricing 
Test Method
Exome Sequencing with CNV Detection
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 11517 | NLRP12 | 81479 | 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.
Clinical Features and Genetics
Clinical Features
Familial Cold Autoinflammatory Syndrome 2 (FCAS2) is a disorder characterized by recurrent episodic fevers triggered by exposure to cold temperature or mild physical injury with bouts occurring monthly and lasting between 2-10 days. Other symptoms include myalgia, urticaria and occasionally headaches, sensorineural hearing loss, buccal aphthous ulcers, and lymphadenopathy. Symptom onset occurs during the first days of life (Jeru et al. 2011). Unlike Muckle Wells Syndrome and Familial Mediterranean Fever, amyloidosis has not been reported in patients with FCAS2. Genetic testing is helpful in distinguishing different forms of periodic fever syndromes and for employing appropriate therapeutic intervention during attacks (Touitou et al. 2013, Caso et al. 2013).
Genetics
FCAS2 is inherited in an autosomal dominant manner through mutations in the NLRP12 gene. Since identification of NLRP12 in FCAS2 in 2008, only 7 causative mutations have been identified with missense mutations being most prevalent (5 of 7) followed by splice site alterations (1 of 7) and non-sense mutations (1 of 7) (Jeru et al. 2011; Jeru et al. 2008). No deletions have been reported in the NLRP12 gene to date (Touitou et al. 2004). FCAS2 is fully penetrant with symptoms occurring in the first few months of life. The NLRP12 protein regulates proinflammatory responses through inhibition of nuclear factor kappa B and activation of proinflammatory caspases which in turn convert interleukin 1B into its active form (Wang et al. 2002; Kinoshita et al. 2005).
Clinical Sensitivity - Sequencing with CNV PGxome
Analytical sensitivity should be high because all causative mutations reported to date are detectable by sequencing. Clinical sensitivity cannot be estimated because only a small number of cases have been reported.
Testing Strategy
This test provides full coverage of all coding exons of the NLRP12 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 features consistent with periodic fever syndromes and elevated C-reactive protein levels are candidates for testing (Jeru et al. 2011). Ideal candidates have a family history of the disease.
Individuals with clinical features consistent with periodic fever syndromes and elevated C-reactive protein levels are candidates for testing (Jeru et al. 2011). Ideal candidates have a family history of the disease.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| NLRP12 | 609648 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Familial Cold Autoinflammatory Syndrome 2 | AD | 611762 |
Citations
- Caso F, Rigante D, Vitale A, Lucherini OM, Costa L, Atteno M, Compagnone A, Caso P, Frediani B, Galeazzi M, Punzi L, Cantarini L. 2013. Monogenic Autoinflammatory Syndromes: State of the Art on Genetic, Clinical, and Therapeutic Issues. International Journal of Rheumatology 2013: 1–15. PubMed ID: 24282415
- Jéru I, Borgne G Le, Cochet E, Hayrapetyan H, Duquesnoy P, Grateau G, Morali A, Sarkisian T, Amselem S. 2011. Identification and functional consequences of a recurrent NLRP12 missense mutation in periodic fever syndromes. Arthritis & Rheumatism 63: 1459–1464. PubMed ID: 21538323
- Jeru I, Duquesnoy P, Fernandes-Alnemri T, Cochet E, Yu JW, Lackmy-Port-Lis M, Grimprel E, Landman-Parker J, Hentgen V, Marlin S, McElreavey K, Sarkisian T, Grateau G, Alnemri ES, Amselem S. 2008. Mutations in NALP12 cause hereditary periodic fever syndromes. Proceedings of the National Academy of Sciences 105: 1614–1619. PubMed ID: 18230725
- Kinoshita T, Wang Y, Hasegawa M, Imamura R, Suda T. 2005. PYPAF3, a PYRIN-containing APAF-1-like Protein, Is a Feedback Regulator of Caspase-1-dependent Interleukin-1 Secretion. Journal of Biological Chemistry 280: 21720–21725. PubMed ID: 15817483
- Touitou I, Galeotti C, Rossi-Semerano L, Hentgen V, Piram M, Koné-Paut I, CeRéMAI, French reference center for autoinflammatory diseases. 2013. The expanding spectrum of rare monogenic autoinflammatory diseases. Orphanet journal of rare diseases 8: 162 PubMed ID: 24131530
- Touitou I, Lesage S, McDermott M, Cuisset L, Hoffman H, Dode C, Shoham N, Aganna E, Hugot J-P, Wise C, Waterham H, Pugnere D, Demaille J, Sarrauste de Menthiere C. 2004. Infevers: An evolving mutation database for auto-inflammatory syndromes. Human Mutation 24: 194–198. PubMed ID: 15300846
- Wang L, Manji GA, Grenier JM, Al-Garawi A, Merriam S, Lora JM, Geddes BJ, Briskin M, DiStefano PS, Bertin J. 2002. PYPAF7, a Novel PYRIN-containing Apaf1-like Protein That Regulates Activation of NF-kappa B and Caspase-1-dependent Cytokine Processing. Journal of Biological Chemistry 277: 29874–29880. PubMed ID: 12019269
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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2) Select Additional Test Options
No Additional Test Options are available for this test.