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Hyper IgE Syndrome Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
DOCK8 81479,81479
PGM3 81479,81479
SPINK5 81479,81479
STAT3 81479,81479
TYK2 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10169Genes x (5)81479 81479(x10) $990 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our Custom Panel tool.

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).

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.


Genetic Counselors


  • Megan Piazza, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Hyper-IgE Syndrome (HIES), also known as Job’s syndrome and Buckley’s syndrome, is characterized by a triad of symptoms including recurrent staphylococcal abscesses, recurrent airway infections, and increased immunoglobin E (>2000 U/ml) in serum (Szczawinska-Poplonyk et al., 2011. PMID: 22085750). HIES presents during childhood and with variable expressivity. There are both autosomal dominant (AD-HIES) and recessive forms (AR-HIES) of the disorder. AD-HIES affects about 1 in 100,000 people with patients being more prone to candidiasis, cyst forming pneumonia, connective tissue and skeletal abnormalities, retained primary teeth, and hyper-extensibility in joints. AR-HIES is distinguished from AD-HIES by increased occurrence and severity of viral infections such as Herpes simplex, Herpes zoster, and Molluscum contagiosum. AR-HIES patients are also more susceptible to food allergies, hemolytic anemia, vasculitis, and have a higher frequency of neurological complications including encephalitis, and vascular brain lesions. Connective and bone abnormalities are typically not observed in AR-HIES (Szczawinska-Poplonyk et al., 2011. PMID: 22085750).

TYK2 deficiency is very rare, only reported in two families, with patients presenting with HIES-like symptoms (Kilic et al., 2012).

Netherton Syndrome, which affects about 1 in 200,000 newborns, has similar skin features and elevated IgE levels to AD-HIES. These patients also present with fragile hair, ichthyosis linearis circumflexa, and failure to thrive (Sprecher et al., 2001. PMID: 11511292).

Genetic testing is helpful in the differential diagnosis of HIES subtypes and from other similar disorders including Omenn Syndrome, common variable immunodeficiency, atopic dermatitis, chronic granulomatous disease, and aspergillosis.


AD-HIES is completely penetrant and caused by pathogenic variants in the STAT3 gene with de novo pathogenic variants being frequently found. The autosomal recessive form (AR-HIES) is phenotypically similar, but due to pathogenic variants in the DOCK8 or PGM3 genes (Szczawinska-Poplonyk et al., 2011. PMID: 22085750; Sassi et al., 2014. PubMed ID: 24698316).

Netherton Syndrome and TYK2 deficiency are inherited in an autosomal recessive manner through pathogenic variants in the SPINK5 and TYK2 genes respectively (Kilic et al., 2012. PMID: 22402565; Sprecher et al., 2001. PMID: 11511292; Bitoun et al., 2002. PMID: 11841556).

AD-HIES represents 60-70% of all HIES cases with many being due to sporadic pathogenic variants. See individual gene test descriptions for information on molecular biology of gene products.

Clinical Sensitivity - Sequencing with CNV PGxome

Pathogenic variants in the STAT3 gene are identified in 60% of cases of Autosomal Dominant Hyper IgE Syndrome. Analytical sensitivity is >95% by Sanger sequencing (Schimke et al. 2010. PMID: 20816194). In a study of 60 families with 82 patients with Autosomal Recessive Hyper IgE Syndrome (AR-HIES), pathogenic variants in the DOCK8 gene were found in 78% of cases. Of those patients, gross deletions ranging from a single exon to the whole gene were found in 32 of 64 patients (Engelhardt et al. 2015., PMID: 25724123). Analytical sensitivity is therefore about ~50% for detection of pathogenic variants in the DOCK8 gene as deletions encompassing one or more exon are not generally detected by sequencing. SPINK5 analytical sensitivity is >95% as gross deletions in the SPINK5 gene have only been reported in one case (Hachem et al., 2006. PMID: 16601670). In two separate studies of patients with confirmed Netherton Syndrome diagnosis, pathogenic variants in the SPINK5 gene were found in 14 of 19, and 21 of 21 individuals respectively (Sprecher et al., 2001. PMID: 11511292; Bitoun et al., 2002. PMID: 11841556).

In a study of 60 families with 82 patients with AR-HIES, pathogenic variants in the DOCK8 gene were found in 78% of cases. Of those patients, gross deletions ranging from a single exon to the whole gene were found in 32 of 64 patients (Engelhardt et al., 2015). Analytical sensitivity is therefore about ~50% for detection of pathogenic variants in the DOCK8 gene. Gross deletions in the STAT3 and SPINK5 genes have only been reported in a few cases (Schimke et. al., 2010. PMID: 20816194; Hachem et al., 2006. PMID: 16601670). A deletion encompassing the PGM3, UBE3D, ME1, and SNAP91 genes has been reported in a patient with immunodeficiency and skeletal dysplasia (Stray-Pedersen et al., 2014. PubMed ID: 24931394).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes 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 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, eczema, recurrent lung infections, and staphylococcal abscesses. (Szczawinska-Poplonyk et al., 2011. PMID: 22085750).


Official Gene Symbol OMIM ID
DOCK8 611432
PGM3 172100
SPINK5 605010
STAT3 102582
TYK2 176941
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test



  • Bitoun et al., 2002. PubMed ID: 11841556
  • Engelhardt et al., 2015. PubMed ID: 25724123
  • Hachem et al., 2006. PubMed ID: 16601670
  • Kilic et al., 2012. PubMed ID: 22402565
  • Sassi et al., 2014. PubMed ID: 24698316
  • Schimke et al., 2010. PubMed ID: 20816194
  • Sprecher et al., 2001. PubMed ID: 11511292
  • Stray-Pedersen et al., 2014. PubMed ID: 24931394
  • Szczawinska-Poplonyk et al., 2011. PubMed ID: 22085750


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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View Ordering Instructions

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2) Select Additional Test Options

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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