• Test code: 08136
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit

Invitae Radiation-Sensitive Severe Combined Immunodeficiency (SCID) Panel

Test description

The Invitae Radiation-Sensitive Severe Combined Immunodeficiency (SCID) Panel analyzes 4 genes that are associated with severe combined immunodeficiency (SCID) as well as increased sensitivity to ionizing radiation. This test is useful for the diagnosis of patients who are suspected of having RS-SCID from clinical symptoms and laboratory findings. Genetic testing of the genes in this panel 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.

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Primary panel (4 genes)

Radiation-Sensitive Severe Combined Immunodeficiency (RS-SCID) including:

Gene Disorder Protein name Protein symbol
DCLRE1C DCLRE1C (Artemis) deficiency Artemis Artemis
LIG4 DNA ligase IV deficiency DNA ligase IV LIG4
NHEJ1 Cernunnos/XLF deficiency Cernunnos Cernunnos
PRKDC DNA PKcs deficiency DNA-PKcs DNA-PKcs

Severe combined immunodeficiency syndrome (SCID) is an infantile-onset primary immunodeficiency syndrome that results in the dysfunction of both T-lymphocyte and B-lymphocyte function. Some causes of SCID may also result in defective natural killer cell function.

Children with SCID often present with severe, recurrent, and often life-threatening infections that are difficult to treat due to the patient’s compromised immune system. These infections may be caused by opportunistic organisms that are not usually infectious to children with normal immune systems; they can even be caused by vaccines made with a live virus. Patients often have persistent diarrhea, which can lead to a failure to thrive and skin involvement such as recurrent skin infections or rashes. Some patients with milder mutations in SCID-associated genes may be characterized as Omenn syndrome. Patients with Omenn syndrome develop erythroderma, hepatosplenomegaly, and lymphadenopathy in addition to immunodeficiency, and may have T-cells that function poorly. Without treatment, patients with SCID often die early in life, so early diagnosis and treatment are crucial. Many patients have been treated successfully with hematopoietic stem cell transplant.

Radiation-sensitive SCID (RS-SCID) has the same signs and symptoms of generalized SCID, with the additional caveat that a subset of cells from these individuals show increased radiosensitivity. This condition is also known as Athabaskan-type SCID due to its increased prevalence in Athabaskan-speaking Navajo and Apache Native Americans. Some patients may present with an isolated antibody deficiency, in which case they need to avoid exposure to radiation and live vaccination. Hematopoietic stem cell transplantation should also be considered earlier in disease progression for these individuals.

DCLRE1C, LIG4, NHEJ1, PRKDC are the only genes known to be associated with RS-SCID. However, due to the rarity of this condition, the percent of RS-SCID attributed to pathogenic variants in these genes is currently unknown.

Radiation-sensitive SCID is inherited in an autosomal recessive manner.

According to recent newborn screening data, RS-SCID has an estimated incidence rate of 1 in 1,500,000 in the US. Incidence is as high as 1 in 3,500 in individuals of Navajo heritage due to a founder mutation in DCLRE1C.

This test may be considered for individuals:

  • who have abnormal newborn screening results for SCID
  • who have combined immunodeficiency in peripheral blood
  • AND who also show signs of increased sensitivity to ionizing radiation

Assay and technical information

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
DCLRE1C NM_001033855.2
LIG4 NM_002312.3
NHEJ1 NM_024782.2
PRKDC NM_006904.6