Hyper-IgM Syndrome (HIGM): Four-gene Profile (AICDA, UNG, CD40, CD40LG) (Full Gene Sequencing)

CPT: 81404; 81479
Updated on 1/24/2018
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Test Details

Test Includes

This test covers all coding nucleotides of genes AICDA, UNG, CD40, and CD40L, plus at least two and typically 20 flanking intronic nucleotides upstream and downstream of each coding exon, covering the conserved donor and acceptor splice sites, as well as typically 20 flanking nucleotides in the 5′ and 3′ UTR.


Confirm a clinical diagnosis of HIGM; detect carriers; allow early diagnosis in family members


This method does not reliably detect mosaic variants; large deletions; large duplications, inversions, or other rearrangements; or deep intronic variants. It may be affected by allele-dropout, it may not allow determination of the exact numbers of T/A or microsatellite repeats, and it does not allow any conclusion as to whether two heterozygous variants are present on the same or on different chromosome copies.

Results of this test are for investigational purposes only. The performance characteristics of this assay have been determined by LabCorp. The result should not be used as a diagnostic procedure without confirmation of the diagnosis by another medically established diagnostic product or procedure.


DNA sequencing

Reference Interval

Normal equals reference sequence or variants that are known or predicted to be benign; abnormal equals all other variants.

Additional Information

Hyperimmunoglobulin M syndrome (HIGM) is a recessively (X-linked or autosomal) inherited immune disorder characterized by lack of IgG, IgA, and IgE in the presence of excess IgM, leading to increased susceptibility to bacterial infections. In HIGM type 1 and 3, cellular immunity is also affected, resulting in additional susceptibility to opportunistic pathogens. In HIGM types 2 and 5, patients are at increased risk of autoimmunity. Mutations in CD40LG, AICDA, CD40, and UNG account for all HIGM1, 2, 3, and 5, respectively, and about 60% of HIGM overall. Genetic testing can confirm a clinical diagnosis of HIGM, identify the HIGM subtype present, and detect mutation carriers within affected families.

Specimen Requirements


Whole blood; DNA is accepted (Call 800-345-4363 for DNA collection information.)


2 mL


Lavender-top (EDTA) tube


Samples may be stored for brief periods at 4°C. Ship overnight at room temperature.

Storage Instructions

Maintain specimen at room temperature.

Causes for Rejection

Container broken or leaking; container not labeled or label not legible; use of improper anticoagulant

Clinical Information

Special Instructions

Test orders must include an attestation that the provider has the patient's informed consent for genetic testing. See sample physician office consent form: Consent for Genetic Testing. In the case of family tests (ie, known mutations), please submit the result report of the first patient tested in the family (the index case), if not performed at a LabCorp facility. Other family members are subsequently tested for the specific mutation found in the first patient tested.


Durandy A, Revy P, Imai K, et al. Hyper-immunoglobulin M syndromes caused by intrinsic B-lymphocyte defects. Immunol Rev. 2005 Feb; 203:67-79.15661022
Lougaris V, Badolato R, Ferrari S, et al. Hyper immunoglobulin M syndrome due to CD40 deficiency: Clinical, molecular, and immunological features. Immunol Rev. 2005; 203:48-66.15661021

For Providers

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