Test Catalog

Test ID: IBDGP    
Inflammatory Bowel Disease Primary Immunodeficiency (PID) Panel

Useful For Suggests clinical disorders or settings where the test may be helpful

Identifying variants in genes known to be associated with monogenic inflammatory bowel disease (IBD) or IBD-like conditions. Identification may allow for development of a specific treatment and surveillance plan for these patients based on the molecular alteration identified, and predictive testing of at-risk family members.

 

Diagnosis of monogenic IBD or IBD-like conditions among patients with early onset or very-early onset IBD, or who are refractory to conventional therapy.

 

Ascertaining carrier status of family members of individuals diagnosed with early onset IBD for genetic counseling purposes. If a family member has already tested positive for a variant in a gene on this panel, order known variant analysis (KVAR). See Advisory Information section (Specimen tab) for more details.

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test uses next-generation sequencing to test for variants in the ADA, ADAM17, AICDA, BTK, CD3G, CD40LG, CTLA4, CYBA, CYBB, DCLRE1C (Artemis), DKC1, DOCK8, FOXP3, G6PC3, ICOS, IKBKG, IL10, IL10RA, IL10RB, IL21, IL21R, IL2RA, IL2RG, ITGB2, LIG4, LRBA, MEFV, MVK, NCF2, NCF4, NLRC4, PIK3CD, PIK3R1, PLCG2, RAG1, RAG2, RTEL1, SH2D1A, SKIV2L, SLC37A4, STAT1, STAT3, STIM1, STXBP2, TNFAIP3, TTC37, TTC7A, WAS, WIPF1, XIAP and ZAP70 genes.

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

For skin biopsy or cultured fibroblast specimens, fibroblast culture and cryopreservation testing will be performed at an additional charge. If viable cells are not obtained, the client will be notified.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Inflammatory bowel disease (IBD) is a term used to encompass disorders involving chronic intestinal inflammation. These conditions are typically classified as either Crohn's disease or ulcerative colitis based on clinical features, colonoscopy findings, histologic changes, and the anatomical distribution of disease; however, in some cases, overlapping features are noted. Over the past few decades, the incidence of inflammatory bowel disease has been rapidly increasing in both children and adults. Common symptoms include: diarrhea, abdominal pain, fatigue, and unintentional weight loss. The majority of IBD is thought to be either polygenic or multifactorial. In these susceptible individuals, an environmental component appears to trigger disease manifestation. However, in rare cases, IBD or IBD-like intestinal inflammation can be attributed to disease-causing variants in a single gene (monogenic inheritance) which results in a highly penetrant condition.

 

Monogenic IBD typically presents at a very young age (often <6 years of age at onset of symptoms) compared to polygenic IBD (peak at 20-40 years of age), although the incidence of polygenic IBD in young patients is increasing and conversely some patients with milder forms of monogenic IBD may not present until later. Individuals with polygenic or monogenic IBD may also have other family members affected with IBD (a positive family history). In many cases, patients with a monogenic form of IBD may not respond well to conventional treatment modalities and may have a related primary immunodeficiency. Identification of the genetic cause of disease in these individuals is important as it may change the treatment plan for these individuals. Depending on the genetic cause, targeted therapies or allogeneic hematopoietic stem cell transplantation may be beneficial. Therefore, identification of these conditions is important as it can guide treatment, including medical therapy, surgery, or stem cell transplant, and may reduce the high morbidity and mortality associated with these conditions.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

Evaluation and categorization of variants is performed using the most recent published American College of Medical Genetics and Genomics (ACMG) recommendations as a guideline. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

 

Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and predictions made by these tools may change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgment.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Clinical Correlations:

Some individuals who have involvement of 1 or more of the genes on the panel may have a variant that is not identified by the methods performed (eg, promoter variants, deep intronic variants). The absence of a variant, therefore, does not eliminate the possibility of disease.

 

Test results should be interpreted in context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

For predictive testing of asymptomatic individuals, it is often useful to first test an affected family member. Identification of a pathogenic variant in an affected individual allows for more informative testing of at-risk individuals.

 

Technical Limitations:

Next-generation sequencing may not detect all types of genetic variants. The variant detection software has lower detection efficiency for insertion/deletion variants as compared to single nucleotide variants. Therefore, small deletions and insertions greater than 8 nucleotides in length may not be detected by this test. Copy number variations (CNV) are not currently reported for any of the genes on this panel. Additionally, rare variants may be present that could lead to false-negative or false-positive results. In some cases, DNA variants of undetermined significance may be identified. If results do not match clinical findings, consider alternative methods for analyzing these genes, such as Sanger sequencing or large deletion/duplication analysis. 

If the patient has had an allogeneic blood or bone marrow transplant or a recent (ie, <6 weeks from time of sample collection) heterologous blood transfusion, results may be inaccurate due to the presence of donor DNA. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

 

Reclassification of Variants-Policy:

At this time, it is not standard practice for the laboratory to systematically review likely deleterious alterations or variants of uncertain significance that are detected and reported. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time. Consultation with a healthcare provider, or team of healthcare providers, with expertise in genetics and primary immunodeficiencies, is recommended for interpretation of this result.

 

Contact the laboratory if additional information is required regarding the transcript or human genome assembly used for the analysis of this patient's results.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Uhlig HH, Schwerd T, Koletzko S, et al: The Diagnostic Approach to Monogenic Very Early Onset Inflammatory Bowel Disease. Gastroenterology 2014;147:990-1007

2. Uhlig HH, Schwerd T: From Genes to Mechanisms: The Expanding Spectrum of Monogenic Disorders Associated with Inflammatory Bowel Disease. Inflamm Bowel Dis. 2016;22:202-212

3. Kelsen JR, Baldassano RN, Artis D, et al: Maintaining intestinal health: the genetics and immunology of very early-onset inflammatory bowel disease. Cell Mol Gastroenterol Hepatol 2015;1:462-476

Special Instructions Library of PDFs including pertinent information and forms related to the test