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HelpTest Code SCIDP Severe Combined Immunodeficiency (SCID) Gene Panel, Varies
Ordering Guidance
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 this testing option, call 800-533-1710.
Shipping Instructions
Specimen Required
Patient Preparation: A previous bone marrow transplant from an allogeneic donor will interfere with testing. For information about testing patients who have received a bone marrow transplant, call 800-533-1710.
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Green top (sodium heparin)
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
3. Whole blood collected postnatal from an umbilical cord is also acceptable. See Additional Information
Specimen Stability Information: Ambient 4 days (preferred)/Refrigerated 4 days/Frozen 4 days
Additional Information:
1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for specimens received after 4 days, and DNA yield will be evaluated to determine if testing may proceed.
2. To ensure minimum volume and concentration of DNA are met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.
3. For postnatal umbilical cord whole blood specimens, maternal cell contamination studies are recommended to ensure test results reflect that of the patient tested. A maternal blood specimen is required to complete maternal cell contamination studies. Order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on both the cord blood and maternal blood specimens under separate order numbers.
Specimen Type: Saliva
Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.
Supplies:
DNA Saliva Kit High Yield (T1007)
Saliva Swab Collection Kit (T786)
Container/Tube:
Preferred: High-yield DNA saliva kit
Acceptable: Saliva swab
Specimen Volume: 1 Tube if using T1007 or 2 swabs if using T786
Collection Instructions: Collect and send specimen per kit instructions.
Specimen Stability Information: Ambient (preferred) 30 days/Refrigerated 30 days
Additional Information: Saliva specimens are acceptable but not recommended. Due to lower quantity/quality of DNA yielded from saliva, some aspects of the test may not perform as well as DNA extracted from a whole blood sample. When applicable, specific gene regions that were unable to be interrogated will be noted in the report. Alternatively, additional specimen may be required to complete testing.
Specimen Type: Blood spot
Supplies: Card-Blood Spot Collection (Filter Paper) (T493)
Container/Tube:
Preferred: Collection card (Whatman Protein Saver 903 Paper)
Acceptable: PerkinElmer 226 filter paper or blood spot collection card
Specimen Volume: 2 to 5 Blood spots
Collection Instructions:
1. An alternative blood collection option for a patient older than 1 year is a fingerstick. For detailed instructions, see How to Collect a Dried Blood Spot Sample.
2. Let blood dry on the filter paper at ambient temperature in a horizontal position for a minimum of 3 hours.
3. Do not expose specimen to heat or direct sunlight.
4. Do not stack wet specimens.
5. Keep specimen dry.
Send: Ambient (preferred)/Refrigerated
Additional Information:
1. Blood spot specimens are acceptable but not recommended. Due to lower quantity/quality of DNA yielded from blood spots, some aspects of the test may not perform as well as DNA extracted from a whole blood sample. When applicable, specific gene regions that were unable to be interrogated will be noted in the report. Alternatively, additional specimen may be required to complete testing.
2. Due to lower concentration of DNA yielded from blood spot, it is possible that additional specimen may be required to complete testing.
3. For collection instructions, see Blood Spot Collection Instructions
4. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777)
5. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800)
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: Ambient (preferred) <24 hours/Refrigerated <24 hours
Additional Information:
1. Specimens are preferred to be received within 24 hours of collection.
2. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks are required to culture fibroblasts before genetic testing can occur.
Specimen Type: Cultured fibroblasts
Source: Skin or tissue
Container/Tube: T-25 flask
Specimen Volume: 2 Flasks
Collection Instructions: Submit confluent cultured fibroblast cells from a biopsy. Cultured cells from a prenatal specimen will not be accepted.
Specimen Stability Information: Ambient (preferred) <24 hours/Refrigerated <24 hours
Additional Information:
1. Specimens are preferred to be received within 24 hours of collection. Culture and/or extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.
2. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks are required to culture fibroblasts before genetic testing can occur.
Specimen Type: Extracted DNA
Container/Tube:
Preferred: Screw Cap Micro Tube, 2mL with skirted conical base
Acceptable: Matrix tube, 1mL
Collection Instructions:
1. The preferred volume is at least 100 mcL at a concentration of 75 ng/mcL.
2. Include concentration and volume on tube.
Specimen Stability Information: Frozen (preferred) 1 year/Ambient/Refrigerated
Additional Information: DNA must be extracted in a CLIA-certified laboratory or equivalent and must be extracted from a specimen type listed as acceptable for this test (including applicable anticoagulants). Our laboratory has experience with Chemagic, Puregene, Autopure, MagnaPure, and EZ1 extraction platforms and cannot guarantee that all extraction methods are compatible with this test. If testing fails, one repeat will be attempted, and if unsuccessful, the test will be reported as failed and a charge will be applied. If applicable, specific gene regions that were unable to be interrogated due to DNA quality will be noted in the report.
Forms
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 in:
-Informed Consent for Genetic Testing (T576)
Useful For
Establishing a diagnosis of a severe combined immunodeficiency (SCID) associated with known causal genes
Identifying variants within genes known to be associated with SCID, allowing for predictive testing of at-risk family members and/or determination of targeted management (anticipatory guidance, management changes, specific therapies)
Genetics Test Information
This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 50 genes associated with severe combined immunodeficiency (SCID): ADA, AK2, ATM, BCL11B, CARD11, CD247, CD3D, CD3E, CD3G, CD8A, CHD7, CIITA, CORO1A, DCLRE1C, DOCK2, DOCK8, EXTL3, FOXN1, IKZF1, IL2RA, IL2RG, IL7R, JAK3, LAT, LCP2, LIG4, MTHFD1, NBN, NHEJ1, ORAI1, PAX1, PNP, POLE2, PRKDC, PTPRC, RAC2, RAG1, RAG2, RFX5, RFXANK, RFXAP, RMRP, SEMA3E, SMARCAL1, STIM1, TBX1, TTC7A, WAS, WIPF1, and ZAP70. See Targeted Genes and Methodology Details for Severe Combined Immunodeficiency (SCID) Gene Panel for details regarding the targeted gene regions evaluated by this test.
Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, recurrence risk assessment, familial screening, and genetic counseling for SCID.
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| CULFB | Fibroblast Culture for Genetic Test | Yes | No |
| MATCC | Maternal Cell Contamination, B | Yes | No |
Testing Algorithm
For skin biopsy or cultured fibroblast specimens, a fibroblast culture will be performed at an additional charge. If viable cells are not obtained, the client will be notified.
For postnatal umbilical cord blood specimens that have an accompanying maternal blood specimen, maternal cell contamination studies will be performed at an additional charge.
Special Instructions
Method Name
Sequence Capture and Amplicon-Based Next-Generation Sequencing (NGS)/Quantitative Real-Time Polymerase Chain Reaction (qPCR) and Sanger Sequencing as needed
Reporting Name
SCID Gene PanelSpecimen Type
VariesSpecimen Minimum Volume
See Specimen Required
Specimen Stability Information
| Specimen Type | Temperature | Time |
|---|---|---|
| Varies | Varies | |
Reject Due To
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.Clinical Information
Severe combined immunodeficiency (SCID) is characterized by the absence or dysfunction of T lymphocytes, which affects both cellular and humoral adaptive immunity. This absence or dysfunction of T cells results in a severe form of inherited primary immunodeficiency that may be life-threatening. SCID typically presents in infancy with persistent respiratory and gastrointestinal infections, failure to thrive, or graft-versus-host disease (due to engraftment of maternal T cells). The absence of lymphoid tissue, immunoglobulins, and B lymphocytes may also be noted.
Critically, having low T-cell numbers is not sufficient on its own for a diagnosis of SCID because other non-SCID disorders, such as thymic defects, may also present with significant T-cell lymphopenia. SCID results from genetic causes of hematopoietic stem cell intrinsic defects in T-lymphocyte development. Primary thymic function defects should be differentiated from SCID because hematopoietic stem cell transplantation is unlikely to be curative for thymic function defects, as the defect is in thymic stromal cell development, not in hematopoietic stem cells.
Severe combined immunodeficiency is suspected when the patient has fewer than 300 autologous CD3 T cells per microliter and additional suggestive features, such as having less than 20% of CD4+ cells with naive cell surface markers, an abnormal SCID newborn screen, a family history of SCID, recurrent or opportunistic infections, or features of Omenn syndrome. An important diagnostic criterion for typical SCID is having less than 50 autologous CD3 T cells per microliter in blood, which requires immediate medical intervention. Other diagnostic criteria may include the identification of a disease-causing variant or variants in a gene whose product is known to be essential for T-cell development and having no alternate explanation for low T-cell count and low to undetectable TREC (T cell receptor excision circles) or <20% of CD4 T cells with naive cell surface marker CD45RA. Alternatively, the presence of maternal T cells in peripheral blood due to failure to reject transplacentally transferred cells is a pathognomonic finding.
Atypical or "leaky" SCID is the term used for patients with partial defects in T-cell number and function. Leaky SCID tends to present in patients older than 12 months of age with recurrent, severe, and prolonged viral infections, bronchiectasis, failure to thrive, and autoimmune manifestations, including cytopenias. Patients may display partial or restricted antigen-specific antibody responses. Leaky SCID is often caused by hypomorphic variants in genes normally associated with typical SCID. Leaky SCID can be diagnosed based on the following: low T-cell number for age; oligoclonal T cells; abnormal TREC or <20% of CD4+ T cells that are naive; the identification of disease-causing variants identified in a gene whose product is known to be essential for T-cell development; reduced T-cell proliferation tests (defined as a proliferative response to phytohemagglutinin, anti-CD3, or anti-CD3/CD28); and the exclusion of other SCID or combined immunodeficiency conditions with a known genotype, thymic disorder, and other disorders associated with low T-cell numbers.
Omenn syndrome, a form of leaky SCID that typically presents in infancy, is characterized by erythroderma, alopecia, hepatosplenomegaly, and lymphadenopathy. Laboratory findings may include elevated IgE, eosinophilia, and lymphocytosis. While RAG1 and RAG2 hypomorphic variants are most often associated with leaky SCID or Omenn syndrome, patients may have variants affecting other genes and the proteins they produce, such as Artemis or interleukin-7 receptor (IL-7R) alpha. There are forms of leaky SCID with hypomorphic variants in these genes that do not have the associated Omenn syndrome phenotype.
Severe combined immunodeficiency can be classified as T-B- or T-B+ SCID, with further subdivision possible based on the presence or absence of natural killer (NK) cells. T-B- SCID is typically caused by a defect in V(D)J recombination, the process that creates the antigen receptor diversity critical to the adaptive immune system. However, T-B- SCID may also be caused by certain enzyme deficiencies, such as adenosine deaminase deficiency, which results in accumulation of metabolic by-products that are toxic to lymphocytes. Reticular dysgenesis-the most severe form of combined immunodeficiency-is caused by a deficiency of the enzyme adenylate kinase 2 and genetic variants in the AK2 gene. Reticular dysgenesis is characterized by a T-B-NK- phenotype, congenital agranulocytosis, lymphopenia, lymphoid and thymic hypoplasia, and bilateral sensorineural deafness.
T-B+ SCID is characterized by impaired development of mature T-cells and the presence of nonfunctional B cells. It is most often caused by genetic variants that affect cytokine-mediated signaling. X-linked T-B+ SCID is due to variants in the IL2RG gene, which encodes the common gamma chain that is a part of the IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21 receptors. Autosomal recessive forms of T-B+ SCID due to variants in JAK3 or IL7R also disrupt cytokine signaling. Genetic variants in one of the four CD3 genes (CD3G, CD3D, CD3E, and CD247[CD3Z]) inhibit CD3 signaling and cause T-B+ SCID.
The T-B+ cellular phenotype may also be caused by thymic defects that must be differentiated from T-B+ SCID to guide treatment decisions as stated above. Causes of these thymic defects include coronin-1A deficiency, which causes disruption of thymic egress of T cells and defective T-cell locomotion, and CD45 deficiency caused by variants in the PTPRC gene. Thymic defects with additional congenital anomalies may be observed in DiGeorge syndrome (represented on this panel by TBX1), CHARGE (coloboma, heart defects, atresia choanae [also known as choanal atresia], growth retardation, genital abnormalities, and ear abnormalities) syndrome (due to variants in CHD7 or SEMA3E), and patients with genetic variants in FOXN1.
Reference Values
An interpretive report will be provided.
Day(s) Performed
Varies
Report Available
28 to 42 daysSpecimen Retention Time
Whole blood: 28 days (if available); Extracted DNA: 3 months, Saliva: 30 days (if available); Blood spots: 1 year (if available)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 |
|---|---|---|
| SCIDP | SCID Gene Panel | 107540-7 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 620135 | Test Description | 62364-5 |
| 620136 | Specimen | 31208-2 |
| 620137 | Source | 31208-2 |
| 620138 | Result Summary | 50397-9 |
| 620139 | Result | 82939-0 |
| 620140 | Interpretation | 69047-9 |
| 620141 | Additional Results | 48767-8 |
| 620142 | Resources | 99622-3 |
| 620143 | Additional Information | 48767-8 |
| 620144 | Method | 85069-3 |
| 620145 | Genes Analyzed | 82939-0 |
| 620146 | Disclaimer | 62364-5 |
| 620147 | Released By | 18771-6 |