Hyper-IgE Syndrome NGS Panel

  • Panel Description
  • Test Description
  • CPT Codes
  • Resources

Panel Description

Netherton Syndrome
PGM3 Deficiency 
TYK2 Deficiency

Hyper-IgE syndrome (HIES) is a rare primary immunodeficiency disorder characterized by eczema and recurrent skin rash, elevated serum IgE, recurrent staphylococcal skin abscesses, eosinophilia, and recurrent lung infections. There are two primary forms of HIES categorized by whether they have autosomal dominant (AD-HIES) or autosomal recessive (AR-HIES) inheritance patterns.

AD-HIES is the more common form and is associated with pathogenic variants in the STAT3 gene. Variants in this gene are also linked to onychomycosis and mucocutaneous candidiasis. AR-HIES is associated with DOCK8 deficiency and is often distinguished by recurring viral infections. This type also has an increased risk for neurological disorders.

In addition to AD-HIES and AR-HIES, this panel includes genes associated with other conditions that may result in elevated serum IgE levels, such as Netherton syndrome, PGM3 deficiency, and TYK2 deficiency.

This panel may be appropriate for anyone with a personal or family history of HIES. Individuals with elevated serum IgE, recurrent skin and lung infections, unexplained bone deformities, and eczema may benefit from testing.

Genetic testing can help establish a HIES diagnosis and determine the specific etiology. Analysis of the genes associated with HIES helps with prognosis and treatment development.

Genetic testing for Hyper-IgE syndrome can:
  • Establish or confirm the appropriate diagnosis
  • Identify risks for additional related symptoms
  • Assist in modifying lifestyle changes
  • Result in more personalized treatment and symptom management
  • Inform family members about their own risk factors
  • Provide options for family planning

Test Description

  • Sequencing
  • Del/Dup
  • Rush / STAT
  • Exclude VUS
  • MCC
  • Duo/Trio
3-5 weeks
Call for details
DOCK8, PGM3, SPINK5, STAT3, TYK2 ( 5 genes )
96% at 20x
Blood (two 4ml EDTA tubes, lavender top) or Extracted DNA (3ug in EB buffer) or Buccal Swab or Saliva (kits available upon request)
All sequencing technologies have limitations. This analysis is performed by Next Generation Sequencing (NGS) and is designed to examine coding regions and splicing junctions. Although next generation sequencing technologies and our bioinformatics analysis significantly reduce the contribution of pseudogene sequences or other highly-homologous sequences, these may still occasionally interfere with the technical ability of the assay to identify pathogenic variant alleles in both sequencing and deletion/duplication analyses. Sanger sequencing is used to confirm variants with low quality scores and to meet coverage standards. If ordered, deletion/duplication analysis can identify alterations of genomic regions which include one whole gene (buccal swab specimens and whole blood specimens) and are two or more contiguous exons in size (whole blood specimens only); single exon deletions or duplications may occasionally be identified, but are not routinely detected by this test. Identified putative deletions or duplications are confirmed by an orthogonal method (qPCR or MLPA). This assay will not detect certain types of genomic alterations which may cause disease such as, but not limited to, translocations or inversions, repeat expansions (eg. trinucleotides or hexanucleotides), alterations in most regulatory regions (promoter regions) or deep intronic regions (greater than 20bp from an exon). This assay is not designed or validated for the detection of somatic mosaicism or somatic mutations.

CPT Code 81479x2

NOTE:  The CPT codes listed on the website are in accordance with Current Procedural Terminology, a publication of the American Medical Association. CPT codes are provided here for the convenience of our clients. Clients who bill for services should make the final decision on which codes to use.


Hyper-IgE Syndrome