IL-12 Receptor B1 Deficiency via the IL12RB1 Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
1768 IL12RB1$1220.00 81479 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity

In a study of 141 patients with IL12RB1 deficiency, pathogenic variants in the IL12RB1 gene were found in 94% of cases. Analytical sensitivity is >95% as gross deletions have only been reported in a few cases (van de Vosse et al. 2013; de Beaucoudrey et al. 2010).

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 IL12RB1$690.00 81479 Add to Order
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Turnaround Time

The great majority of tests are completed within 28 days.

Clinical Features

Interleukin 12 receptor B1 (IL12RB1) deficiency is the most prevalent type of Mendelian susceptibility to mycobacterial disease (MSMD) and immunodeficiency syndrome. Affected patients display infection with poorly virulent bacteria nontuberculous Mycobacteria, nontyphoidal Salmonella and Candida albicans with symptom onset occurring around 3 years of age (Elloumi-Zghal et al. 2002). In a study of 132 patients with IL12RB1 deficiency, Bacille Calmette-Guerin disease occurred in 75% of individuals vaccinated with the bacterium and several developed disseminated disease. Salmonella and Candida albicans infections occurred in 43% and 24% of individuals. In 15% of cases, disseminated infections were fatal with average age of death being 8 years old. Interestingly, patients display broad resistance to other infectious agents beyond Mycobacterium and Salmonella (de Beaucoudrey et al. 2010). Genetic testing is helpful in the differential diagnosis of IL12RB1 deficiency from other MSMDs including interferon gamma receptor deficiencies, ectodermal dysplasia with immunodeficiency, and STAT1 deficiency (Bustamante et al. 2014).


IL12RB1 deficiency is inherited in an autosomal recessive manner through pathogenic variants in the IL12RB1 gene. The majority of pathogenic variants reported to date result in loss of IL12RB1 surface expression. In a few cases, nonfunctional IL12RB1 surface receptors have been found (Fieschi et al. 2004). Splice site, missense, nonsense, and small insertions/deletions account for 27%, 24%, 20%, and 26% of pathogenic variants in the IL12RB1 gene. Pathogenic variants occur throughout the entire gene except exons 16 and 17 near the c-terminal end (van de Vosse et al. 2013; de Beaucoudrey et al. 2010). Gross deletions are reported in about 3% of cases. Penetrance is not complete with about 12% of individuals being asymptomatic (van de Vosse et al. 2013). The IL12RB1 gene encodes the IL12 receptor B2 chain which is a subunit of both the IL12 and IL23 receptors. Upon binding their respective cytokines, IL12 and IL23 signaling activate Interferon gamma expression to ward off infection (Altare et al. 1998).

Testing Strategy

This test involves bidirectional Sanger sequencing using genomic DNA of all coding exons of the IL12RB1 gene plus ~10 bp of flanking non-coding DNA on each side. We will also sequence any single exon (Test #100) or pair of exons (Test #200) in patients and relatives of patients or to confirm research results.

Indications for Test

Candidates for testing include individuals with BCM disease, nontyphoidal Salmonellosis, or Candida albicans infections. Affected individuals exhibit decreased interferon gamma secretion in response to infection to these select pathogens. Ideal candidates have flow cytometry displaying loss of IL12RB1 receptor expression (de Beaucoudrey et al. 2010; van de Vosse et al. 2013).


Official Gene Symbol OMIM ID
IL12RB1 601604
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
IL12RB1 Deficiency 614891


Genetic Counselors
  • Altare F, Durandy A, Lammas D, Emile J-F, Lamhamedi S, Deist F Le, Drysdale P, Jouanguy E, Döffinger R, Bernaudin F, Jeppsson O, Gollob JA, Meinl E, Segal AW, Fischer A, Kumararatne D, Casanova JL. 1998. Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency. Science 280: 1432–1435. PubMed ID: 9603732
  • Bustamante J, Boisson-Dupuis S, Abel L, Casanova J-L. 2014. Mendelian susceptibility to mycobacterial disease: Genetic, immunological, and clinical features of inborn errors of IFN-γ immunity. Seminars in Immunology 26: 454–470. PubMed ID: 25453225
  • de Beaucoudrey L, Samarina A, Bustamante J, Cobat A, Boisson-Dupuis S, Feinberg J, Muhsen S Al-, Jannière L, Rose Y, Suremain M de, Kong X-F, Filipe-Santos O, Chapgier A, Picard C, Fischer A, Dogu F, Ikinciogullari A, Tanir G, Al-Hajjar S, Al-Jumaah S, Frayha HH, AlSum Z, Al-Ajaji S, Alangari A, Al-Ghonaium A, Adimi P, Mansouri D, Ben-Mustapha I, Yancoski J, Garty BZ, Rodriguez-Gallego C, Caragol I, Kutukculer N, Kumararatne DS, Patel S, Doffinger R, Exley A, Jeppsson O, Reichenbach J, Nadal D, Boyko Y, Pietrucha B, Anderson S, Levin M, Schandené L, Schepers K, Efira A, Mascart F, Matsuoka M, Sakai T, Siegrist CA, Frecerova K, Blüetters-Sawatzki R, Bernhöft J, Freihorst J, Baumann U, Richter D, Haerynck F, De Baets F, Novelli V, Lammas D, Vermylen C, Tuerlinckx D, Nieuwhof C, Pac M, Haas WH, Müller-Fleckenstein I, Fleckenstein B, Levy J, Raj R, Cohen AC, Lewis DB, Holland SM, Yang KD, Wang X, Wang X, Jiang L, Yang X, Zhu C, Xie Y, Lee PP, Chan KW, Chen TX, Castro G, Natera I, Codoceo A, King A, Bezrodnik L, Di Giovani D, Gaillard MI, de Moraes-Vasconcelos D, Grumach AS, da Silva Duarte AJ, Aldana R, Espinosa-Rosales FJ, Bejaoui M, Bousfiha AA, Baghdadi JE, Ozbek N, Aksu G, Keser M, Somer A, Hatipoglu N, Aydogmus C, Asilsoy S, Camcioglu Y, Gülle S, Ozgur TT, Ozen M, Oleastro M, Bernasconi A, Mamishi S, Parvaneh N, Rosenzweig S, Barbouche R, Pedraza S, Lau YL, Ehlayel MS, Fieschi C, Abel L, Sanal O, Casanova JL. 2010. Revisiting Human IL-12Rβ1 Deficiency: A Survey of 141 Patients From 30 Countries. Medicine 89: 381–402. PubMed ID: 21057261
  • Elloumi-Zghal H, Barbouche MR, Chemli J, Béjaoui M, Harbi A, Snoussi N, Abdelhak S, Dellagi K. 2002. Clinical and genetic heterogeneity of inherited autosomal recessive susceptibility to disseminated Mycobacterium bovis bacille calmette-guerin infection. Journal of Infectious Diseases 185: 1468–1475. PubMed ID: 11992283
  • Fieschi C. 2004. A novel form of complete IL-12/IL-23 receptor 1 deficiency with cell surface-expressed nonfunctional receptors. Blood 104: 2095–2101. PubMed ID: 15178580
  • van de Vosse E, Haverkamp MH, Ramirez-Alejo N, Martinez-Gallo M, Blancas-Galicia L, Metin A, Garty BZ, Sun-Tan Ç, Broides A, Paus RA de, Keskin Ö, Çagdas D, Tezcan I, Lopez-Ruzafa E, Aróstegui JI, Levy J, Espinosa-Rosales FJ, Sanal Ö, Santos-Argumedo L, Casanova JL, Boisson-Dupuis S, van Dissel JT, Bustamante J. 2013. IL-12Rβ1 Deficiency: Mutation Update and Description of the IL12RB1 Variation Database. Human Mutation 34: 1329–1339. PubMed ID: 23864330
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

Deletion/Duplication Testing via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

Order Kits

Ordering Options

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.
  • 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.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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