X-linked Severe Combined Immunodeficiency via the IL2RG Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7897 IL2RG 81405 81405,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7897IL2RG81405 81405(x1), 81479(x1) $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Megan Piazza, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Severe combined immunodeficiency (SCID) affects one in 75,000 births and is a heterogeneous disorder that arises through genetic defect in genes associated with lymphocyte development and function. To date, there are over 20 genes known to cause SCID through an autosomal recessive manner, with mutations in the IL2RG gene being the only X-linked form of the disease (Allenspach et al. 2013). Categorization of T-cell, B-cell and Natural Killer (NK) cell levels are used to distinguish between subtypes of SCID, but genetic testing is essential in specifically defining the molecular defect leading to disease. X-linked SCID accounts for 40-50% cases of SCID with patients showing impaired B-cell function and diminished T-cell and NK cell levels. SCID due to mutations in the JAK3 or IL7R genes is phenotypically identical to X-SCID. X-SCID is characterized by failure to thrive, absence of tonsils/lymph nodes, candidiasis, recurrent and persistent infections due to cellular and humoral immunodeficiency. Bone marrow transplant or gene therapy is required to correct disease with patients succumbing to disease by two years of age without therapeutic intervention (Gaspar et al. 2013). Genetic testing can also be used to distinguish X-SCID from other X-linked immunodeficiencies including agammaglobulinemia (Test #1650), Wiskott-Aldrich syndrome (Test #440), and hyper IgM syndrome (Test #1613). Infants with human immunodeficiency virus infection may also mirror symptoms of X-SCID (Allenspach et al. 2013).

Genetics

There are 23 monogenic causative genes involved with autosomal recessive forms of SCID. Mutation in the IL2RG gene is the only X-linked form of SCID. Female carriers are asymptomatic. Nearly 200 mutations have been described throughout the IL2RG gene with exons 3-5 being hotspots. Missense mutations are found most frequently (40%) followed by nonsense (24%), splice site alterations (19%), and small insertions/deletions (17%) with each mutation type being fully penetrant for disease (Puck et al. 1997; Piirilä et al. 2006). Maternal mosaicism for IL2RG mutations exists in ~13% cases of X-SCID. Similarly, somatic reversion in subsets of immune precursor cells have been reported to result in patients with variable clinical phenotype (Speckmann et al. 2008). The IL2RG gene encodes the common gamma chain of the interleukin receptor 2, a key membrane receptor required for cytokine signaling to promote T-cell, B-cell, and NK cell development (Noguchi et al. 1993; Allenspach et al. 2013).

Clinical Sensitivity - Sequencing with CNV PG-Select

Two independent reports identified mutations in the IL2RG gene in 87 of 103 patients presenting with X-SCID (Puck et al. 1997). Analytical sensitivity to detect mutations within the IL2RG gene using this methodology is >95% (Hacein-Bey et al. 1996).

Gross deletions have only been reported in a single case of X-SCID (Hacein-Bey et al. 1996).

Testing Strategy

This test provides full coverage of all coding exons of the IL2RG gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for testing include patients with lack of thymic shadow on chest radiograms, flow cytometric analysis indicating marked decrease in T-cell and Natural Killer cell numbers, impaired B-cell function, and clinical features consistent with X-SCID. Screening showing low T-cell receptor excision circles from blood spots is also diagnostic hallmark of X-linked SCID (Allenspach et al. 2013).

Gene

Official Gene Symbol OMIM ID
IL2RG 308380
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
X-Linked Severe Combined Immunodeficiency XL 300400

Related Tests

Name
Common Variable Immune Deficiency/IgA Deficiency via the TNFRSF13B Gene
Familial Hemophagocytic Lymphohistiocytosis (FHL) Panel
Primary Immunodeficiency via the PIK3CD Gene

Citations

  • Allenspach E, Rawlings DJ, Scharenberg AM. 2013. X-Linked Severe Combined Immunodeficiency. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301584
  • Gaspar HB, Qasim W, Davies EG, Rao K, Amrolia PJ, Veys P. 2013. How I treat severe combined immunodeficiency. Blood 122: 3749–3758. PubMed ID: 24113871
  • Hacein-Bey H, Cavazzana-Calvo M, Deist F Le, Dautry-Varsat A, Hivroz C, Riviere I, Danos O, Heard JM, Sugamura K, Fischer A, others. 1996. gamma-c gene transfer into SCID X1 patients’ B-cell lines restores normal high-affinity interleukin-2 receptor expression and function. Blood 87: 3108–3116. PubMed ID: 8605324
  • Noguchi M, Nakamura Y, Russell SM, Ziegler SF, Tsang M, Cao X, Leonard WJ. 1993. Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor. Science 262: 1877–1880. PubMed ID: 18941169
  • Piirilä H, Väliaho J, Vihinen M. 2006. Immunodeficiency mutation databases (IDbases). Hum. Mutat. 27: 1200–1208. PubMed ID: 17004234
  • Puck JM, Pepper AE, Henthorn PS, Candotti F, Isakov J, Whitwam T, Conley ME, Fischer RE, Rosenblatt HM, Small TN, others. 1997. Mutation analysis of IL2RG in human X-linked severe combined immunodeficiency. Blood 89: 1968–1977. PubMed ID: 9058718
  • Speckmann C, Pannicke U, Wiech E, Schwarz K, Fisch P, Friedrich W, Niehues T, Gilmour K, Buiting K, Schlesier M, Eibel H, Rohr J, et al. 2008. Clinical and immunologic consequences of a somatic reversion in a patient with X-linked severe combined immunodeficiency. Blood 112: 4090–4097. PubMed ID: 18728247

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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