Autosomal Dominant Hyper IgE Syndrome via the STAT3 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 | |
|---|---|---|---|---|---|
| 11719 | STAT3 | 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
Autosomal dominant Hyper IgE Syndrome (AD-HIES), also known as Job’s Syndrome and Buckley’s Syndrome, is characterized by recurrent staphylococcal abscesses, recurrent airway infections, and increased immunoglobin E (>2000 U/ml) in serum (Szczawinska-Poplonyk et al 2011). Secondary symptoms may include eczema, eosinophilia, cellulitis, recurrent bone fractures, abnormal development of permanent teeth and ocular complications. AD-HIES, the more prominent form of HIES, is symptomatically similar to the recessive form of the disease (AR-HIES). AD-HIES can be distinguished from AR-HIES genetically by mutations in the STAT3 (AD-HIES) and DOCK8 (AR-HIES) genes. Clinically AD-HIES is associated with facial, dental, and connective tissue abnormalities while AR-HIES exhibits fungal or viral cutaneous infections and early onset malignancies (Buckley 2001). AD-HIES affects an estimated 1 in 100,000 individuals. Early antibiotic intervention during infection episodes is important as disease progresses rapidly from minor to major infections (Sowerwine et al. 2012).
Genetics
AD-HIES is an autosomal dominant disorder with complete penetrance caused by mutations in the STAT3 gene. De novo mutations are frequently found. The autosomal recessive form (AR-HIES) is phenotypically similar but due to mutations in the DOCK8 gene (Szczawinska-Poplonyk et al 2011). Missense mutations predominantly found within the STAT3 DNA binding and SH2 domains account for the majority of document causative mutations (Holland et al 2007). Large deletions are rarely found and have only been shown to occur in frame (Schimke et al 2010). Nonsense and frameshift mutations have not been reported within the STAT3 gene, and complete deletion in mouse models results in embryonic lethality (Shen et al. 2004). Signal transducer and activator of transcription (STAT3) is involved in cytokine and growth factor receptors signaling and serves as a transcription factor to regulate several cellular functions including cell growth and apoptosis (Mogensen 2013). Conditional mouse models lacking STAT3 display heightened inflammatory responses and underline the importance of this protein in regulation of immune responses (Willson et al. 2013; Kane et al. 2014).
Clinical Sensitivity - Sequencing with CNV PGxome
Mutations in the STAT3 gene are identified in 60% of cases of AD-HIES. Analytical sensitivity is 95% by Sanger sequencing (Schimke et al. 2010).
Testing Strategy
This test provides full coverage of all coding exons of the STAT3 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 this test are patients showing IgE levels higher than 2000 U/ml and a weighted score of clinical features >30 (Szczawinska-Poplonyk et al 2011).
Candidates for this test are patients showing IgE levels higher than 2000 U/ml and a weighted score of clinical features >30 (Szczawinska-Poplonyk et al 2011).
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| STAT3 | 102582 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Hyperimmunoglobulin E Syndrome | AD | 147060 |
Citations
- Buckley RH. 2001. The hyper-IgE syndrome. Clin Rev Allergy Immunol 20: 139–154. PubMed ID: 11269224
- Holland SM, DeLeo FR, Elloumi HZ, Hsu AP, Uzel G, Brodsky N, Freeman AF, Demidowich A, Davis J, Turner ML, Anderson VL, Darnell DN, et al. 2007. STAT3 mutations in the hyper-IgE syndrome. N. Engl. J. Med. 357: 1608–1619. PubMed ID: 17881745
- Kane A, Deenick EK, Ma CS, Cook MC, Uzel G, Tangye SG. 2014. STAT3 is a central regulator of lymphocyte differentiation and function. Curr. Opin. Immunol. 28C: 49–57. PubMed ID: 24594518
- Mogensen TH. 2013. STAT3 and the Hyper-IgE syndrome: Clinical presentation, genetic origin, pathogenesis, novel findings and remaining uncertainties. JAKSTAT 2: e23435. PubMed ID: 24058807
- Schimke LF, Sawalle-Belohradsky J, Roesler J, Wollenberg A, Rack A, Borte M, Rieber N, Cremer R, Maass E, Dopfer R, Reichenbach J, Wahn V, et al. 2010. Diagnostic approach to the hyper-IgE syndromes: immunologic and clinical key findings to differentiate hyper-IgE syndromes from atopic dermatitis. J. Allergy Clin. Immunol. 126: 611–617.e1. PubMed ID: 20816194
- Shen Y, Schlessinger K, Zhu X, Meffre E, Quimby F, Levy DE, Darnell JE Jr. 2004. Essential role of STAT3 in postnatal survival and growth revealed by mice lacking STAT3 serine 727 phosphorylation. Mol. Cell. Biol. 24: 407–419. PubMed ID: 14673173
- Sowerwine KJ, Holland SM, Freeman AF. 2012. Hyper-IgE syndrome update. Ann. N. Y. Acad. Sci. 1250: 25–32. PubMed ID: 22268731
- Szczawinska-Poplonyk A, Kycler Z, Pietrucha B, Heropolitanska-Pliszka E, Breborowicz A, Gerreth K. 2011. The hyperimmunoglobulin E syndrome--clinical manifestation diversity in primary immune deficiency. Orphanet J Rare Dis 6: 76. PubMed ID: 22085750
- Willson TA, Jurickova I, Collins M, Denson LA. 2013. Deletion of intestinal epithelial cell STAT3 promotes T-lymphocyte STAT3 activation and chronic colitis following acute dextran sodium sulfate injury in mice. Inflamm. Bowel Dis. 19: 512–525. PubMed ID: 23429443
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
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