Hyper IgM Syndrome Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
2689 AICDA 81479,81479 Order Options and Pricing
ATM 81408,81479
BTK 81406,81479
CD40 81479,81479
CD40LG 81404,81479
MRE11 81479,81479
NBN 81479,81479
NFKBIA 81479,81479
PIK3CD 81479,81479
SH2D1A 81404,81403
UNG 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
2689Genes x (11)81479 81403, 81404, 81406, 81408, 81479 $890 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 PGxome Custom Panel tool.

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.

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

Hyper IgM syndrome (HIGM) is due to impaired immunoglobulin class switch recombination (CSR) resulting in an increase in IgM and a decreased IgG, IgA and IgE antibody levels. This humoral immunodeficiency leads to recurrent sinopulmonary infections, chronic diarrhea due to Cryptosproidium infection, and neutropenia presenting within the first or second decade of life. In severe cases, patients may also present with, sclerosing cholangitis, chronic arthritis, thrombocytopenia, hemolytic anemia, hypothyroidism, kidney disease and failure to thrive (Davies and Thrasher. 2010. PubMed ID: 20180797; Etzioni and Ochs. 2004. PubMed ID: 15319456; Leven et al. 2016. PubMed ID: 27189378). About 75% of HIGM cases are inherited in an X-linked recessive manner due to pathogenic variants in the CD40LG gene (HIGM1). Three autosomal recessive forms of HIGM have been described through pathogenic variants in the AICDA (HIGM2), CD40 (HIGM3), and UNG (HIGM5) genes. A fourth autosomal recessive form of HIGM is described with no known genetic cause to date (HIGM4) (Johnson et al. 2013. PubMed ID: 20301576). HIGM may also be present in complex disorders including ataxia telangiectasia, agammaglobulinemia, Nijmegen breakage syndrome, combined immundeficiencies, and common variable immunodeficiency. Treatment for HIGM includes prophylactic IgG and antibiotics. Genetic testing is also helpful in the differential diagnosis of HIGM from other disorders including congenital rubella syndrome, lymphoma and acquired autoimmune diseases (Davies and Thrasher. 2010. PubMed ID: 20180797; Conley et al. 2009. PubMed ID: 19302039).

Genetics

HIGM1 is inherited in an X-linked manner through pathogenic variants in the CD40LG gene. HIGM can also be inherited in an autosomal recessive manner through pathogenic variants in the AICDA, CD40, or UNG genes. There is a fourth autosomal recessive form of HIGM (termed HIGM4) where the underlying genetic defect is still unknown. About 75% of HIGM cases to date are due to pathogenic variants in the CD40LG gene (Johnson et al. 2013. PubMed ID: 20301576).

Other syndromes inherited in an X-linked recessive manner that also exhibit increased IgM levels include agammaglobulinemia (BTK), and lymphoproliferative syndrome (SH2D1A). Related autosomal dominant disorders include primary immunodeficiency (PIK3CD) and ectodermal dysplasia (NFKBIA). Autosomal recessive conditions include ataxia telangiectasia (ATM), Nijmegen breakage syndrome (NBN), and ataxia telangiectasia like disorder (MRE11) (Conley et al. 2009. PubMed ID: 19302039).

See individual gene test descriptions for information on molecular biology of gene products and mutation spectra.

Clinical Sensitivity - Sequencing with CNV PGxome

In a molecular study of 140 patients presenting with Hyper IgM syndrome (HIGM) based on recurrent and/or severe infections, elevated IgM, and reduced IgA and IgG levels, sequencing of the CD40LG, CD40, NEMO, AICDA, UNG, ICOS, ICOSL, BTK, and SH2D1 genes was performed. Pathogenic variants were found in 103 of 140 patients with pathogenic variants in the CD40LG, AICDA, UNG, NEMO, and BTK genes accounting for 92%, 4%, 1%, 1%, and 3% of cases respectively (Lee et al. 2005. PubMed ID: 15358621). Analytical sensitivity for the CD40, MRE11, NBN, NFKBIA, and PIK3CD genes should be high as all reported variants to date are detectable by sequencing. Gross deletions have been reported in the ATM, AICDA, and CD40LG genes, but represent less than 10% of cases (Gatti and Perlman. 2016. PubMed ID: 20301790; Durandy et al. 2006. PubMed ID: 16964591; Lee et al. 2005. PubMed ID: 15358621; Johnson et al. 2013. PubMed ID: 20301576). SH2D1A deletions have been reported in 25% of cases (Sumegi et al. 2000. PubMed ID: 11049992). Analytical sensitivity is >90% for the BTK gene with large deletions, duplications, and rearrangements being present in less than 8% of XLA cases (Conley et al. 1998. PubMed ID: 9545398; Kanegane et al. 2001. PubMed ID: 11742281).

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 full coverage as >20X NGS reads or Sanger sequencing.

In addition to the regions described above, this testing includes coverage of the following variants that reside in untranslated or deep intronic regions: ATM: c.2639-384A>G, c.3994-159A>G, and c.5763-1050A>G; BTK: c.-169T>G, c.1567-23A>G; and CD40LG: c.347-915A>T variants.

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

HIGM is hallmarked by recurrent respiratory infections within the first years of life. Laboratory findings consistent with HIGM include normal or heightened IgM and reduced IgG, IgA and IgE levels, lack of antibody response to protein or polysaccharide antigens, reduced memory (CD27+) B cells and absence of switched memory (IgD-CD27+) B cells (Davies and Thrasher. 2010. PubMed ID: 20180797; Etzioni and Ochs. 2004. PubMed ID: 15319456; Leven et al. 2016. PubMed ID: 27189378; Conley et al. 2009. PubMed ID: 19302039).

Genes

Official Gene Symbol OMIM ID
AICDA 605257
ATM 607585
BTK 300300
CD40 109535
CD40LG 300386
MRE11 600814
NBN 602667
NFKBIA 164008
PIK3CD 602839
SH2D1A 300490
UNG 191525
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Conley et al. 1998. PubMed ID: 9545398
  • Conley et al. 2009. PubMed ID: 19302039
  • Davies and Thrasher. 2010. PubMed ID: 20180797
  • Durandy et al. 2006. PubMed ID: 16964591
  • Etzioni and Ochs. 2004. PubMed ID: 15319456
  • Gatti and Perlman. 2016. PubMed ID: 20301790
  • Johnson et al. 2013. PubMed ID: 20301576
  • Kanegane et al. 2001. PubMed ID: 11742281
  • Lee et al. 2005. PubMed ID: 15358621
  • Leven et al. 2016. PubMed ID: 27189378
  • Sumegi et al. 2000. PubMed ID: 11049992

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

loading Loading... ×

ORDER OPTIONS

View Ordering Instructions

1) Select Test Type


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.

Total Price: $
×
Copy Text to Clipboard
×