Test Code: 9493

Early onset Inflammatory Bowel Disease: Sequencing Panel
Test Code: 9493
Turnaround time: 6 weeks

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 50 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.

CEN4GEN 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 of 48 known genes 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
AICDA, BTK, CD40LG, CYBA, CYBB, DCLRE1C, FOXP3, HPS1, HPS4, HPS6, ICOS, IL10RA, IL2RA, LRBA, MEFV, MVK, NCF2, NCF4, PTEN, RET, SH2D1A, SLC37A4, STXBP2, TTC37, WAS, XIAP

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 mean 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

Submit only 1 of the following specimen types

Type: Whole Blood
Specimen Requirements:
In EDTA (purple top) tube: Infants (2 years): 3-5 ml
Older Children & Adults: 5-10 ml.

Specimen Collection and Shipping: Ship sample at room temperature with overnight delivery.

Type: Isolated DNA
Specimen Requirements: In microtainer: 60 μg
Isolation using the QiagenTM Puregene kit for DNA extraction is recommended.

Specimen Collection and Shipping: Refrigerate until time of shipment in 100 ng/ul of TE buffer. Ship sample at room temperature with overnight delivery.

RELATED TESTS

  • IBD Targeted Hotspot Panel