A recent study (Q Li, CH Lee, LA Peters, et al. Gastroenterol 2016; 150: 1196-1207) provides a description of a new genetic variant causing very early onset inflammatory bowel disease (VEOIBD), which designates cases of IBD which presents <6 years of age.
Using whole exome sequencing, the authors identified TRIM22 mutations in 3 infants with fistulizing perianal disease and granulomatous colitis. The authors further characterized the defect using functional studies that showed TRIM22 is important in the regulation of nucleotide binding oligomerization domain containing 2 (NOD2)–dependednt activation of interferon-beta signaling and nuclear factor (NF)-κB.
“NOD2 has long been recognized as a critical player in Crohn’s disease pathogenesis, where it is proposed to regulate innate immunity through NF-κB induced proinflammatory responses triggered by peptidoglycan…Simarlarly, mutations in XIAP..are associate with loss of NOD-2-dependent mediated NF-κB signaling” and has a similar phenotype.
My take: Identification of the numerous mutations that lead to VEOIBD is likely to help understand the pathogenesis and ultimately to better therapies.
Related blog posts:
- Just the Beginning: Mutations in Very Early Onset … – gutsandgrowth
- Exome Sequencing in VEO-IBD: More Data | gutsandgrowth