The Invitae T-B-NK+ Severe Combined Immunodeficiency (SCID) Panel analyzes 6 genes that are associated with T-B-NK+ severe combined immunodeficiency. Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of disease-causing variants provide accurate risk assessment and carrier status for at-risk relatives.
DCLRE1C LIG4 NHEJ1 PRKDC RAG1 RAG2
DCLRE1C LIG4 NHEJ1 PRKDC RAG1 RAG2
For a broader analysis of the genetics of severe combined immunodeficiency:
T-cell negative, B-cell negative, NK-cell positive severe combined immunodeficiency (SCID) including:
|Gene||Disorder||Protein name||Protein symbol|
|DCLRE1C||DCLRE1C (Artemis) deficiency||Artemis||Artemis|
|LIG4||DNA ligase IV deficiency||DNA ligase IV||LIG4|
|PRKDC||DNA PKcs deficiency||DNA-PKcs||DNA-PKcs|
|RAG1||RAG 1 deficiency||recombinase activating gene 1||RAG1|
|RAG2||RAG 2 deficiency||recombinase activating gene 2||RAG2|
T-B-NK+ severe combined immunodeficiency (SCID) is an infantile-onset primary immunodeficiency that presents in blood with dysfunction of both T-cells and B-cells, while NK-cells levels remain normal, although non-functional. SCID is characterized by recurrent, overwhelming viral, bacterial and fungal infections and failure to thrive, which if untreated often lead to early death. Less severe mutations in SCID genes cause Omenn syndrome (with or without radiation sensitivity), a disorder characterized by infantile-onset generalized lymphopenia, hypogammaglobulinemia, histiocytosis, diffuse erythroderma/scleroderma, failure to thrive, recurrent infections, chronic diarrhea, lymphadenopathy, alopecia, hepatosplenomegaly, and hypereosinophilia, leading to early death. Features of the RAG-related SCIDs and Omenn syndrome can include the presence of granulomas in several organs like lungs, liver, spleen, lymph nodes, or skin. In DCLRE1C and NHEJ1-related SCID (or Omenn syndrome), patients also present with sensitivity to ionizing radiation (RS-SCID) due to a deficiency of DNA double strand break repair. In NHEJ1-related SCID, patients present, in addition, with microcephaly and growth retardation. In PRKDC-related SCID, additional features reported in some patients include autoimmunity, granulomas, growth failure, dysmorphia, seizures, and profoundly impaired neurological function. LIG4 syndrome is a highly variable disorder with a broad spectrum of severity. Patients can present in infancy with a range of manifestations from RS-SCID to combined immunodeficiency presenting in adolescence. Other features may include pancytopenia, microcephaly, short stature, developmental delay and characteristic facial features. In addition, patients have an increased risk for developing lymphomas and leukemias. However clinically asymptomatic patients with milder immunologic abnormalities and increased sensitivity to ionizing radiation have been reported.
|Gene||% of T-B-NK+ cases attributed|
All causes of T-B-NK+ severe combined immunodeficiency are inherited in an autosomal recessive manner.
T-B-NK+ SCID accounts for approximately 21% of all cases of SCID. The estimated incidence of T-B-NK+ SCID in the US is 1:475,000, based upon data from universal newborn screening (NBS). RS-SCID is found with a very high incidence among Athabascan-speaking native American Indians with an incidence as high as 1 in 3,500 live births in Navajo populations.
This test may be considered for individuals:
For considerations for testing please refer to:
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|