Early Onset Inflammatory Bowel Disease: Sequencing Panel

Condition Description

Inflammatory bowel disease (IBD), encompassing Crohn’s disease, ulcerative colitis, and unclassified IBD (IBDU) is characterized by chronic intestinal inflammation and has multi-factorial etiology with complex interactions between genetic and environmental factors. Although the genetics of IBD is believed to be common and complex, over 150 genetic loci have been described to be associated with IBD. The genetic contribution of the majority of those common loci towards explained heritability or their effect sizes are low. Recent studies have revealed an increasing spectrum of human monogenic diseases with high effect sizes/penetrance that can present with IBD or IBD-like intestinal inflammation. A substantial proportion of patients with those genetic defects present with very early onset intestinal inflammations, particularly if the onset of IBD occurs in subjects less than 10 years of age. There is also considerable overlap between primary immunodeficiency and very early onset IBD. Over 20 monogenic defects/genetic loci have been selected in this genetic diagnostic panel to test for very early onset IBD or IBD-like diseases. In addition to IBD or IBD-like diseases, these monogenic disorders also overlap with immunodeficiency affecting granulocyte and phagocyte activity, hyper- and autoinflammatory disorders, defects with disturbed T and B lymphocyte selection and activation, and defects in immune regulation affecting regulatory T cell activity and interleukin (IL)-10 signaling.
 
EGL is offering a next generation sequencing diagnostic gene panel for very early onset IBD or IBD-like intestinal inflammation. The Inflammatory Bowel Disease Panel will enable the fast, accurate, and cost effective sequencing to:
  • Identify mutation associated very early onset IBD (onset in less than 10 years) or IBD-like diseases
  • Make a molecular diagnosis with the basis of pathogenesis
  • Obtain rationale for patient-specific early intervention with emerging or experimental therapeutics and cell based approaches
  • Screen family members for carrier detection and genetic counseling

References: 
  • Uhling, (2013), Gut, 62: 1795-1805.
  • Zhang and Li, (2014), World J Gastroenterol, 20: 91-99.
  • OMIM

Genes (26)

Your search may have returned a result for a gene alias. Click here for a full list of genes and their aliases.

Indications

This test is indicated for:
  • Confirmation of a clinical diagnosis of inflammatory bowel diseases (IBD).
  • Carrier testing in adults with a family history of inflammatory bowel diseases (IBD).

Methodology

Next Generation Sequencing: In-solution hybridization of all coding exons is performed on the patient's genomic DNA. Although some deep intronic regions may also be analyzed, this assay is not meant to interrogate most promoter regions, deep intronic regions, or other regulatory elements, and does not detect single or multi-exon deletions or duplications. Direct sequencing of the captured regions is performed using next generation sequencing. The patient's gene sequences are then compared to a standard reference sequence. Potentially causative variants and areas of low coverage are Sanger-sequenced. Sequence variations are classified as pathogenic, likely pathogenic, benign, likely benign, or variants of unknown significance. Variants of unknown significance may require further studies of the patient and/or family members.

Detection

Next Generation Sequencing: Clinical Sensitivity: Unknown. Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Large deletions will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient\'s clinical and/or biochemical phenotype.

Analytical Sensitivity: ~99%.

Specimen Requirements

When sample fails to meet the acceptable criteria, please call 470.378.2200 and ask to speak with a laboratory genetic counselor (eglgc@egl-eurofins.com).
Submit only 1 of the following specimen types
Whole Blood (EDTA)
WBP

Requirements
EDTA (Purple Top)
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Collection and Shipping
Ship sample at room temperature for receipt at EGL within 24 hours of collection. Do not refrigerate or freeze.
DNA, Isolated
DNA

Requirements
Microtainer
8µg
Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Collection and Shipping
Refrigerate until time of shipment in 100 ng/µL in TE buffer. Ship sample at room temperature with overnight delivery.
Saliva
SLV

Requirements
Oragene™ Saliva Collection Kit
Orangene™ Saliva Collection Kit used according to manufacturer instructions. Please contact EGL for a Saliva Collection Kit for patients that cannot provide a blood sample.
Collection and Shipping
Please do not refrigerate or freeze saliva sample. Please store and ship at room temperature.
  • IBD Targeted Hotspot Panel
  • Early Onset Inflammatory Bowel Disease: Deletion/Duplication Panel

How to Order