Autosomal Dominant Hyper IgE Syndrome via the STAT3 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
11719 STAT3 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11719STAT381479 81479 $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.

For Reflex to PGxome pricing click here.

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 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

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.

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

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).

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.

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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ORDER OPTIONS

View Ordering Instructions

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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.

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