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Test Code VIRID Viral Susceptibility, Defects in Intrinsic and Innate Immunity, Gene Panel, Varies


Ordering Guidance


For patients with Epstein-Barr virus (EBV) susceptibility or a heritable predisposition to lymphoproliferative diseases, see EBLPD / Epstein-Barr Virus (EBV) Susceptibility and Lymphoproliferative Disorders Gene Panel, Varies.

 

 

Targeted testing for familial variants (also called site-specific or known variants testing) is available for the genes on this panel. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about testing option, call 800-533-1710.



Shipping Instructions


Specimen preferred to arrive within 96 hours of collection.



Specimen Required


Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

 

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated

 

Specimen Type: Skin biopsy

Supplies: Fibroblast Biopsy Transport Media (T115)

Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin.

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient

Additional Information: A separate culture charge will be assessed under CULFB /Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.

 

Specimen Type: Cultured fibroblasts

Container/Tube: T-25 flask

Specimen Volume: 2 Flasks

Collection Instructions: Submit confluent cultured fibroblast cells from a skin biopsy from another laboratory. Cultured cells from a prenatal specimen will not be accepted.

Specimen Stability Information: Ambient (preferred)/Refrigerated (<24 hours)

Additional Information: A separate culture charge will be assessed under CULFB /Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.


Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing (Spanish) (T826)

2. Molecular Genetics: Congenital Inherited Diseases Patient Information (T521)

3. Viral Susceptibility, Lymphoproliferation, and Hemophagocytic Lymphohistiocytosis Patient Information

Secondary ID

619900

Useful For

Providing a comprehensive genetic evaluation for patients with a personal or family history suggestive of an inborn error of immunity causing a hereditary form of severe viral susceptibility

 

Establishing a diagnosis of hereditary form of viral susceptibility, allowing for appropriate management and surveillance for disease features based on the gene and/or variant involved

 

Identifying variants within genes known to be associated with a hereditary form of viral susceptibility, allowing for predictive testing of at-risk family members

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
CULFB Fibroblast Culture for Genetic Test Yes No

Testing Algorithm

For skin biopsy or cultured fibroblast specimens, fibroblast culture will be performed at an additional charge. If viable cells are not obtained, the client will be notified.

Method Name

Sequence Capture and Targeted Next-Generation Sequencing (NGS)

Reporting Name

Viral Susceptibility Gene Panel

Specimen Type

Varies

Specimen Minimum Volume

Blood: 1 mL; Skin biopsy or cultured fibroblasts: See Specimen Required

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Reject Due To

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Clinical Information

Viral infections are common in otherwise healthy individuals, but they may also present clinically due to a primary (genetic) immunodeficiency (ie, inborn error of immunity: IEI). Alternatively, secondary immunodeficiencies may have a similar presentation but result from immunosuppressive medication or illness, such as HIV infection. IEIs may cause a susceptibility to an entire group of pathogens (bacteria, fungi, or viruses), a subset of pathogens (eg, RNA viruses), or can cause susceptibility specific to a single pathogen (eg, Epstein-Barr virus [EBV], human papillomavirus [HPV]). IEIs may also lead to a more severe presentation, including fatal infection caused by a pathogen that usually causes only a mild or non-fatal disease (eg, influenza). This panel targets IEIs that lead to susceptibility to viruses or to a subset of viruses, severe viral pneumonia, or a specific virus. Examples of infections where this gene panel is useful include EBV, skin-tropic beta-HPV, influenza, and SARS-CoV-2. IEIs that lead to systemic immune deficiencies and susceptibility to a large variety of pathogens (eg, T-cell deficiencies) are not included in this panel.

 

EBV is the cause of infectious mononucleosis and persists asymptomatically for life in nearly all adults. It is also associated with the development of T- and B-cell lymphomas, nasopharyngeal and gastric carcinomas, and other malignancies. EBV infection in IEIs can present with fulminant infectious mononucleosis, hemophagocytosis, B-cell proliferative disease (including lymphoma), and hypogammaglobulinemia.

 

Beta-HPVs circulate silently in the general population and cause no visible lesions in most people. Genetic susceptibility to beta-HPVs leads to warts, pityriasis-like lesions, epidermodysplasia verruciformis, and increased risk of non-melanoma skin cancers.

 

Seasonal influenza viruses are common RNA viruses that infect the respiratory tract, causing a benign illness in most infected individuals. Influenza pneumonia or acute respiratory distress syndrome are rare, and the case fatality ratio is less than 1%. Children with severe influenza have been found to carry defects in IRF7, IRF9, STAT1, STAT2, and TLR3. Similarly, the COVID-19 pandemic has revealed that SARS-CoV-2 infection can lead to asymptomatic infection as well as fatal pneumonia. Genetic studies showed that approximately 2 to 3% of cases of severe life-threatening SARS-CoV-2 infection resulted from IEI, mainly genetic defects in the TLR3- or TLR7-dependent type 1 interferon pathway (eg, TLR3, TLR7, IFNAR1/2, STAT2, and IRF7), overlapping with that of severe pneumonia susceptibility in influenza infections.

Reference Values

An interpretive report will be provided.

Interpretation

All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Method Description

Next-generation sequencing (NGS) and/or Sanger sequencing are performed to test for the presence of variants in coding regions and intron/exon boundaries of the genes analyzed, as well as some other regions that have known disease-causing variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for deletions/insertions (delins) less than 40 base pairs (bp), and above 95% for deletions up to 75 bp and insertions up to 47 bp. NGS and/or a polymerase chain reaction-based quantitative method is performed to test for the presence of deletions and duplications in the genes analyzed.

 

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. See Targeted Genes and Methodology Details for Viral Susceptibility, Defects in Intrinsic and Innate Immunity, Gene Panel for details regarding the targeted genes analyzed for each test and specific gene regions not routinely covered.(Unpublished Mayo method)

 

Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.

 

Genes analyzed: CARMIL2, CD27, CD70, CIB1, CTPS1, CXCR4, DBR1, IFIH1, IFNAR1, IFNAR2, IRF3, IRF7, IRF9, MAGT1, POLR3A, POLR3C, PRKCD, RASGRP1, SH2D1A, STAT1, STAT2, TLR3, TLR7, TLR8, TMC6, TMC8, TNFRSF9, TRAF3, UNC93B1, and XIAP

Day(s) Performed

Varies

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information

81443

88233-Tissue culture, skin, solid tissue biopsy (if appropriate)

88240-Cryopreservation (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
VIRID Viral Susceptibility Gene Panel 103742-3

 

Result ID Test Result Name Result LOINC Value
619901 Test Description 62364-5
619902 Specimen 31208-2
619903 Source 31208-2
619904 Result Summary 50397-9
619905 Result 82939-0
619906 Interpretation 69047-9
619907 Additional Results 82939-0
619908 Resources 99622-3
619909 Additional Information 48767-8
619910 Method 85069-3
619911 Genes Analyzed 82939-0
619912 Disclaimer 62364-5
619913 Released By 18771-6