Omenn Syndrome Sequencing Panel

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
Order Kits

NextGen Sequencing

Test Code Test Copy GenesCPT Code Copy CPT Codes
3289 DCLRE1C 81479 Add to Order
IL7R 81479
RAG1 81479
RAG2 81479
Full Panel Price* $640.00
Pricing Comments

We are happy to accommodate requests for single genes or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered on our PGxome Custom Panel.

Targeted Testing

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

Turnaround Time

The great majority of tests are completed within 20 days.

Clinical Sensitivity

Clinical sensitivity is currently unknown. Analytical sensitivity for detection of causative mutations in the IL7R, RAG1, and RAG2 genes is >95% as gross deletions are reported in rare cases (Piirilä et al. 2006). Analytical sensitivity is ~50% for detection of causative variants in the DCLRE1C gene as gross deletions represent about half DCLRE1C mediated SCID cases (Pannicke et al. 2010; Piirilä et al. 2006).

See More

See Less

Del/Dup via aCGH

Test Code Test Copy GenesPriceCPT Code Copy CPT Codes
600 DCLRE1C$990.00 81479 Add to Order
IL7R$990.00 81479
RAG1$990.00 81479
RAG2$990.00 81479
Full Panel Price* $1190.00
Pricing Comments

# of Genes Ordered

Total Price









Over 100

Call for quote

Turnaround Time

The great majority of tests are completed within 20 days.

Clinical Sensitivity

No gross deletions or duplications have been reported in the IL7R gene (Human Gene Mutation Database).

See More

See Less

Clinical Features

Omenn Syndrome (OS), also known as leaky severe combined immunodeficiency (SCID), typically presents during the first year of life and is characterized by erythroderma, desquamation, eosinophilia, failure to thrive, lymphadenopathy and chronic diarrhea. Patients with OS have limited B-cell and elevated T-cell numbers with impaired function resulting in a distinct inflammatory phenotype. OS is primarily due to mutations in the RAG1 and RAG2 genes, but may also be caused through mutations in the IL7R and DCLRE1C/ARTEMIS genes (Villa et al. 2002; Ege et al. 2005; Zago et al. 2014). With variable T-cell populations, diagnosis is often more difficult than classical SCID where T-cells are nearly absent. Interestingly, patients with OS due to DCLRE1C mutations have heightened radiosensitivity which can distinguish these patients from IL7R, RAG1, and RAG2 mediated OS (Ulus-Senguloglu et al. 2012). Primary treatments may include immunosuppressive drugs with hematopoietic stem cell transplants being the only curative option to date (Gaspar et al. 2013). Genetic testing can be helpful in differential diagnosis of OS from other similar disorders including SCID, agammaglobulinemia (Test #1650), Wiskott-Aldrich syndrome (Test #440), histiocytosis, and Netherton syndrome.


OS is inherited in an autosomal recessive manner through mutations in the RAG1, RAG2, DCLRE1C, or IL7R genes (Kalman et al. 2004). Hypomorphic mutations, typically missense, leading to impaired but not complete loss of protein function in the RAG1, RAG2, DCLRE1C, and IL7R genes are the primary cause of OS. Truncating mutations causing complete loss of protein function lead to a more severe SCID phenotype with patients having a near absence of T-cells (Piirilä et al. 2006). RAG1 and RAG2 are the most commonly involved genes with OS. Together the RAG1, RAG2, and DCLRE1C gene products mediate VDJ recombination to facilitate B and T-cell receptor assembly (Moshous et al. 2001; Kalman et al. 2004). The IL7R gene encodes a component of the Interleukin 7 receptor that binds the cytokine, IL7. IL7 signaling stimulates T-cell maturation by promoting differentiation of hematopoietic stem cells into lymphoid progenitors, proliferation of B-cells during maturation, and T and NK cell survival (Puel and Leonard 2000). For further information on the RAG1, RAG2, DCLRE1C, and IL7R genes please refer to the individual test descriptions.

Testing Strategy

For this NGS panel, the full coding regions, plus ~10bp of non-coding DNA flanking each exon, are sequenced for each of the genes listed below. Sequencing is accomplished by capturing specific regions with an optimized solution-based hybridization method, followed by massively parallel sequencing of the captured DNA fragments. Additional Sanger sequencing is performed for any regions not captured or with insufficient number of sequence reads. All pathogenic, undocumented and questionable variant calls are confirmed by Sanger sequencing.

Testing will also cover the deep intronic variant (c.379+288G>A) in the IL7R gene (Butte et al. 2007).

Indications for Test

Patients with severe lymphopenia and lack of adaptive immunity are hallmark indicators of Omenn Syndrome. Typical lab findings include low IgG, IgA, and IgM antibody levels due to near absence of B cell populations. Unlike classical SCID, T cell populations are present at variable levels but are functionally impaired. Recurring infection is also a common symptom of OS patients (Villa et al. 2002). Testing is especially recommended for any newborns identified in T-cell receptor excision circles (TRECs) screening (La Marca et al. 2013). Carrier testing is available for individuals with a family history of the disease.


Official Gene Symbol OMIM ID
DCLRE1C 605988
IL7R 146661
RAG1 179615
RAG2 179616
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Omenn Syndrome 603554

Related Test

Severe Combined Immunodeficiency/Omenn Syndrome via the IL7R Gene


Genetic Counselors
  • Butte MJ, Haines C, Bonilla FA, Puck J. 2007. IL-7 receptor deficient SCID with a unique intronic mutation and post-transplant autoimmunity due to chronic GVHD. Clin. Immunol. 125: 159–164. PubMed ID: 17827065
  • Ege M. 2005. Omenn syndrome due to ARTEMIS mutations. Blood 105: 4179–4186. PubMed ID: 15731174
  • 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
  • Human Gene Mutation Database (Bio-base).
  • Kalman L, Lindegren ML, Kobrynski L, Vogt R, Hannon H, Howard JT, Buckley R. 2004. Mutations in genes required for T-cell development:IL7R, CD45, IL2RG, JAK3, RAG1, RAG2, ARTEMIS, and ADA and severe combined immunodeficiency: HuGE review. Genetics in Medicine 6: 16–26. PubMed ID: 14726805
  • La Marca G, Canessa C, Giocaliere E, Romano F, Duse M, Malvagia S, Lippi F, Funghini S, Bianchi L, Della Bona ML, Valleriani C, Ombrone D, et al. 2013. Tandem mass spectrometry, but not T-cell receptor excision circle analysis, identifies newborns with late-onset adenosine deaminase deficiency. J. Allergy Clin. Immunol. 131: 1604–1610. PubMed ID: 23280131
  • Moshous D, Callebaut I, Chasseval R de, Corneo B, Cavazzana-Calvo M, Deist F Le, Tezcan I, Sanal O, Bertrand Y, Philippe N, Fischer A, Villartay JP de. 2001. Artemis, a novel DNA double-strand break repair/V(D)J recombination protein, is mutated in human severe combined immune deficiency. Cell 105: 177–186. PubMed ID: 11336668
  • Pannicke U, Hönig M, Schulze I, Rohr J, Heinz GA, Braun S, Janz I, Rump E-M, Seidel MG, Matthes-Martin S, Soerensen J, Greil J, et al. 2010. The most frequent DCLRE1C ( ARTEMIS ) mutations are based on homologous recombination events. Human Mutation 31: 197–207. PubMed ID: 19953608
  • Piirilä H, Väliaho J, Vihinen M. 2006. Immunodeficiency mutation databases (IDbases). Hum. Mutat. 27: 1200–1208. PubMed ID: 17004234
  • Puel A, Leonard WJ. 2000. Mutations in the gene for the IL-7 receptor result in T(-)B(+)NK(+) severe combined immunodeficiency disease. Curr. Opin. Immunol. 12: 468–473. PubMed ID: 10899029
  • Ulus-Senguloglu G, Arlett CF, Plowman PN, Parnell J, Patel N, Bourton EC, Parris CN. 2012. Elevated expression of artemis in human fibroblast cells is associated with cellular radiosensitivity and increased apoptosis. British Journal of Cancer 107: 1506–1513. PubMed ID: 23093295
  • Villa A, Sobacchi C, Vezzoni P. 2002. Omenn syndrome in the context of other B cell-negative severe combined immunodeficiencies. Isr. Med. Assoc. J. 4: 218–221. PubMed ID: 11908269
  • Zago CA, Jacob CMA, Albuquerque Diniz EM de, Lovisolo SM, Zerbini MCN, Dorna M, Watanabe L, Fernandes JF, Rocha V, Oliveira JB, Carneiro-Sampaio M. 2014. Autoimmune manifestations in SCID due to IL7R mutations: Omenn syndrome and cytopenias. Human Immunology 75: 662–666. PubMed ID: 24759676
Order Kits

NextGen Sequencing using PG-Select Capture Probes

Test Procedure

We use a combination of Next Generation Sequencing (NGS) and Sanger sequencing technologies to cover the full coding regions of the listed genes plus ~10 bases of non-coding DNA flanking each exon.  As required, genomic DNA is extracted from the patient specimen.  For NGS, patient DNA corresponding to these regions is captured using an optimized set of DNA hybridization probes.  Captured DNA is sequenced using Illumina’s Reversible Dye Terminator (RDT) platform (Illumina, San Diego, CA, USA).  Regions with insufficient coverage by NGS are often covered by Sanger sequencing.

For Sanger sequencing, Polymerase Chain Reaction (PCR) is used to amplify targeted regions.  After purification of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  PCR products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In nearly all cases, cycle sequencing is performed separately in both the forward and reverse directions.

Patient DNA sequence is aligned to the genomic reference sequence for the indicated gene region(s). All differences from the reference sequences (sequence variants) are assigned to one of five interpretation categories, listed below, per ACMG Guidelines (Richards et al. 2015).

(1) Pathogenic Variants
(2) Likely Pathogenic Variants
(3) Variants of Uncertain Significance
(4) Likely Benign Variants
(5) Benign Variants

Human Genome Variation Society (HGVS) recommendations are used to describe sequence variants (  Rare variants and undocumented variants are nearly always classified as likely benign if there is no indication that they alter protein sequence or disrupt splicing.

Analytical Validity

As of March 2016, 6.36 Mb of sequence (83 genes, 1557 exons) generated in our lab was compared between Sanger and NextGen methodologies. We detected no differences between the two methods. The comparison involved 6400 total sequence variants (differences from the reference sequences). Of these, 6144 were nucleotide substitutions and 256 were insertions or deletions. About 65% of the variants were heterozygous and 35% homozygous. The insertions and deletions ranged in length from 1 to over 100 nucleotides.

In silico validation of insertions and deletions in 20 replicates of 5 genes was also performed. The validation included insertions and deletions of lengths between 1 and 100 nucleotides. Insertions tested in silico: 2200 between 1 and 5 nucleotides, 625 between 6 and 10 nucleotides, 29 between 11 and 20 nucleotides, 25 between 21 and 49 nucleotides, and 23 at or greater than 50 nucleotides, with the largest at 98 nucleotides. All insertions were detected. Deletions tested in silico: 1813 between 1 and 5 nucleotides, 97 between 6 and 10 nucleotides, 32 between 11 and 20 nucleotides, 20 between 21 and 49 nucleotides, and 39 at or greater than 50 nucleotides, with the largest at 96 nucleotides. All deletions less than 50 nucleotides in length were detected, 13 greater than 50 nucleotides in length were missed. Our standard NextGen sequence variant calling algorithms are generally not capable of detecting insertions (duplications) or heterozygous deletions greater than 100 nucleotides. Large homozygous deletions appear to be detectable.   

Analytical Limitations

Interpretation of the test results is limited by the information that is currently available.  Better interpretation should be possible in the future as more data and knowledge about human genetics and this specific disorder are accumulated.

When Sanger sequencing does not reveal any difference from the reference sequence, or when a sequence variant is homozygous, we cannot be certain that we were able to detect both patient alleles.  Occasionally, a patient may carry an allele which does not amplify, due to a large deletion or insertion.   In these cases, the report will contain no information about the second allele.  Our Sanger and NGS Sequencing tests are generally not capable of detecting Copy Number Variants (CNVs).

We sequence all coding exons for each given transcript, plus ~10 bp of flanking non-coding DNA for each exon.  Test reports contain no information about other portions of the gene, such as regulatory domains, deep intronic regions or any currently uncharacterized alternative exons.

In most 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 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.

Unless otherwise indicated, DNA sequence data is obtained from a specific cell-type (usually leukocytes from whole blood).   Test reports contain no information about the DNA sequence in other cell-types.

We cannot be certain that the reference sequences are correct.

Rare, low probability interpretations of sequencing results, such as for example the occurrence of de novo mutations in recessive disorders, are generally not included in the reports.

We have confidence in our ability to track a specimen once it has been received by PreventionGenetics.  However, we take no responsibility for any specimen labeling errors that occur before the sample arrives at PreventionGenetics.

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.
loading Loading... ×

Copy Text to Clipboard