Severe Combined Immunodeficiency Panel
Test code: IM0101
The Blueprint Genetics Severe Combined Immunodeficiency Panel is a 68 gene test for genetic diagnostics of patients with clinical suspicion of combined immunodeficiencies.
Approximately half of the cases with severe combined immunodeficiencies (SCIDs) are inherited in X-linked manner (IL2RG), while the inheritance is autosomal recessive for the other half. In addition to typical severe combined immunodeficiencies, this Panel has differential diagnostics power to several other combined immunodeficiencies generally less profound than SCIDs. This Panel is included in the comprehensive Primary Immunodeficiency Panel.
About Severe Combined Immunodeficiency
SCIDs are a group of primary immunodeficiencies characterized by specific mutations in genes of T and B-lymphocyte systems and leading to little or no immune response. Different subtypes of SCIDs are characterized and subdivided by the presence of circulating T and B cells. T cells are abscent or markedly decreased in the most types, but levels of B cells may be vary. In addition, both these disease subgroups (T-B+ and T-B-) can occur with or without NK cells. Patients with SCID are susceptible to recurrent infections, that can be fatal. Worldwide prevalence of SCID is estimated to be at least 1:100 000 births, while some genetically more homogenous populations may show markedly increased numbers. Mutations in IL2RG are the most common reason for SCIDs, explaining circa 50% of all cases and close to 100% of X-linked cases.
Results in 3-4 weeks. We do not offer a maternal cell contamination (MCC) test at the moment. We offer prenatal testing only for cases where the maternal cell contamination studies (MCC) are done by a local genetic laboratory. Read more: http://blueprintgenetics.com/faqs/#prenatal
|ADA||Severe combined immunodeficiency due to adenosine deaminase deficiency||AR||35||88|
|ATM||Breast cancer, Ataxia-Telangiectasia||AD/AR||455||853|
|CARD11||B-cell expansion with NFKB and T-cell anergy, Immunodeficiency||AD/AR||6||8|
|CD40||Immunodeficiency with Hyper-IgM||AR||4||13|
|CD40LG||Immunodeficiency, with hyper-IgM||XL||21||227|
|CIITA||Bare lymphocyte syndrome||AR||6||17|
|DCLRE1C*||Omenn syndrome, Severe combined immunodeficiency with sensitivity to ionizing radiation||AR||16||76|
|DNMT3B||Immunodeficiency-centromeric instability-facial anomalies syndrome||AR||12||46|
|DOCK8||Hyper-IgE recurrent infection syndrome||AR||28||135|
|IKBKG*||Incontinentia pigmenti, Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency, Immunodeficiency, Invasive pneumococcal disease, recurrent, isolated, Osteopetrosis with ectodermal dysplasia and immune defect (OLEDAID)||XL||30||141|
|IL2RA||Interleukin 2 receptor, alpha, deficiency||AR||5||13|
|IL7R||Severe combined immunodeficiency, , T-cell negative, B-cell positive, NK cell positive||AR||15||42|
|ITGB2||Leukocyte adhesion deficiency||AR||27||114|
|JAK3||Severe combined immunodeficiency, , T cell-negative, B cell-positive, natural killer cell-negative||AR||13||56|
|LIG4||Severe combined immunodeficiency with sensitivity to ionizing radiation, LIG4 syndrome||AR||8||36|
|LRBA||Common variable immunodeficiency||AR||10||45|
|MAGT1||Immunodeficiency, with magnesium defect, Epstein-Barr virus infection and neoplasia||XL||4||10|
|NHEJ1||Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation||AR||8||13|
|PMS2*||Mismatch repair cancer syndrome, Colorectal cancer, hereditary nonpolyposis||AD/AR||151||266|
|PNP||Purine nucleoside phosphorylase deficiency||AR||10||34|
|PTPRC||Severe combined immunodeficiency, , T-cell negative, B-cell positive, NK cell positive||AR||4||8|
|RAG1||Omenn syndrome, Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity, T cell-negative, B cell-negative, natural killer cell-positive severe combined immunodeficiency, Combined cellular and humoral immune defects with granulomas||AR||35||168|
|RAG2||Omenn syndrome, Combined cellular and humoral immune defects with granulomas||AR||18||66|
|RFX5||Bare lymphocyte syndrome||AR||5||6|
|RFXANK||MHC class II deficiency||AR||6||12|
|RFXAP||Bare lymphocyte syndrome||AR||5||7|
|RHOH||T-cell immunodeficiency with epidermodysplasia verruciformis||AD/AR||1|
|RMRP||Cartilage-hair hypoplasia, Metaphyseal dysplasia without hypotrichosis, Anauxetic dysplasia||AR||24||119|
|RTEL1||Pulmonary fibrosis and/or bone marrow failure, Dyskeratosis congenita||AD/AR||27||26|
|SMARCAL1||Schimke immunoosseous dysplasia||AR||9||70|
|SP110||Hepatic venoocclusive disease with immunodeficiency||AR||7||10|
|STAT3||Hyper-IgE recurrent infection syndrome, Autoimmune disease, multisystem, infantile onset||AD||27||133|
|STAT4||Behçet disease, Juvenile rheumatoid factor-negative polyarthritis, Oligoarticular juvenile arthritis, Pediatric systemic lupus erythematosus||AD/AR||3|
|STAT5B*||Growth hormone insensitivity with immunodeficiency||AR||5||11|
|STIM1||Stormorken syndrome, Immunodeficiency||AD/AR||10||19|
|STK4||T-cell immunodeficiency syndrome, recurrent infections, autoimmunity,||AR||3||6|
|TAP1||Bare lymphocyte syndrome||AR||2||8|
|TAP2||Bare lymphocyte syndrome||AR||2||13|
|TAPBP||Bare lymphocyte syndrome||AR||1||3|
|TBX1||Conotruncal anomaly face syndrome||AD||7||59|
|TRAC||T-cell receptor-alpha/beta deficiency||AR||1||1|
|WAS||Neutropenia, severe congenital, Thrombocytopenia, Wiskott-Aldrich syndrome||XL||32||429|
|ZAP70||Selective T-cell defect||AR||10||20|
*Some regions of the gene are duplicated in the genome leading to limited sensitivity within the regions. Thus, low-quality variants are filtered out from the duplicated regions and only high-quality variants confirmed by other methods are reported out. Read more.
Gene, refers to HGNC approved gene symbol; Inheritance to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL); ClinVar, refers to a number of variants in the gene classified as pathogenic or likely pathogenic in ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/); HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/). The list of associated (gene specific) phenotypes are generated from CDG (http://research.nhgri.nih.gov/CGD/) or Orphanet (http://www.orpha.net/) databases.
Blueprint Genetics offers a comprehensive Severe Combined Immunodeficiency Panel that covers classical genes associated with CD40 ligand deficiency, combined immunodeficiencies, complement receptor 3 deficiency, DOCK8 deficiency, Job’s syndrome, Omenn syndrome, purine nucleoside phosphorylase PNP deficiency, STAT deficiencies and Wiskott-Aldrich syndrome. The genes are carefully selected based on the existing scientific evidence, our experience and most current mutation databases. Candidate genes are excluded from this first-line diagnostic test. The test does not recognise balanced translocations or complex inversions, and it may not detect low-level mosaicism. The test should not be used for analysis of sequence repeats or for diagnosis of disorders caused by mutations in the mitochondrial DNA.
Analytical validation is a continuous process at Blueprint Genetics. Our mission is to improve the quality of the sequencing process and each modification is followed by our standardized validation process. Average sensitivity and specificity in Blueprint NGS Panels is 99.3% and 99.9% for detecting SNPs. Sensitivity to for indels vary depending on the size of the alteration: 1-10bps (96.0%), 11-20 bps (88.4%) and 21-30 bps (66.7%). The longest detected indel was 46 bps by sequence analysis. Detection limit for Del/Dup (CNV) analysis varies through the genome depending on exon size, sequencing coverage and sequence content. The sensitivity is 71.5% for single exon deletions and duplications and 99% for three exons’ deletions and duplications. We have validated the assays for different starting materials including EDTA-blood, isolated DNA (no FFPE) and saliva that all provide high-quality results. The diagnostic yield varies substantially depending on the used assay, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be cost-effective first line test if your patient’s phenotype is suggestive for a specific mutation profile.
The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. The highest relevance in the reported variants is achieved through elimination of false positive findings based on variability data for thousands of publicly available human reference sequences and validation against our in-house curated mutation database as well as the most current and relevant human mutation databases. Reference databases currently used are the 1000 Genomes Project (http://www.1000genomes.org), the NHLBI GO Exome Sequencing Project (ESP; http://evs.gs.washington.edu/EVS), the Exome Aggregation Consortium (ExAC; http://exac.broadinstitute.org), ClinVar database of genotype-phenotype associations (http://www.ncbi.nlm.nih.gov/clinvar) and the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk). The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (http://sift.jcvi.org), Polyphen (http://genetics.bwh.harvard.edu/pph2/), and Mutation Taster (http://www.mutationtaster.org).
Through our online ordering and statement reporting system, Nucleus, the customer can access specific details of the analysis of the patient. This includes coverage and quality specifications and other relevant information on the analysis. This represents our mission to build fully transparent diagnostics where the customer gains easy access to crucial details of the analysis process.
In addition to our cutting-edge patented sequencing technology and proprietary bioinformatics pipeline, we also provide the customers with the best-informed clinical report on the market. Clinical interpretation requires fundamental clinical and genetic understanding. At Blueprint Genetics our geneticists and clinicians, who together evaluate the results from the sequence analysis pipeline in the context of phenotype information provided in the requisition form, prepare the clinical statement. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals, even without training in genetics.
Variants reported in the statement are always classified using the Blueprint Genetics Variant Classification Scheme modified from the ACMG guidelines (Richards et al. 2015), which has been developed by evaluating existing literature, databases and with thousands of clinical cases analyzed in our laboratory. Variant classification forms the corner stone of clinical interpretation and following patient management decisions. Our statement also includes allele frequencies in reference populations and in silico predictions. We also provide PubMed IDs to the articles or submission numbers to public databases that have been used in the interpretation of the detected variants. In our conclusion, we summarize all the existing information and provide our rationale for the classification of the variant.
A final component of the analysis is the Sanger confirmation of the variants classified as likely pathogenic or pathogenic. This does not only bring confidence to the results obtained by our NGS solution but establishes the mutation specific test for family members. Sanger sequencing is also used occasionally with other variants reported in the statement. In the case of variant of uncertain significance (VUS) we do not recommend risk stratification based on the genetic finding. Furthermore, in the case VUS we do not recommend use of genetic information in patient management or genetic counseling. For some cases Blueprint Genetics offers a special free of charge service to investigate the role of identified VUS.
We constantly follow genetic literature adapting new relevant information and findings to our diagnostics. Relevant novel discoveries can be rapidly translated and adopted into our diagnostics without delay. These processes ensure that our diagnostic panels and clinical statements remain the most up-to-date on the market.
Choose an analysis method
ICD & CPT codes
Commonly used ICD-10 codes when ordering the Severe Combined Immunodeficiency Panel
Accepted sample types
- EDTA blood, min. 1 ml
- Purified DNA, min. 5μg
- Saliva (Oragene DNA OG-500 kit)
Label the sample tube with your patient’s name, date of birth and the date of sample collection.
Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.