From Genes to Mechanisms: The Expanding Spectrum of Monogenic Disorders Associated with Inflammatory Bowel Disease

Inflamm Bowel Dis. 2016 Jan;22(1):202-12. doi: 10.1097/MIB.0000000000000614.


Inborn errors of the intestinal epithelial barrier function as well as the innate and adaptive mucosal immune responses toward the intestinal microbiota are a group of genetic disorders that confer susceptibility to monogenic and syndromal forms of inflammatory bowel disease (IBD). There is a continuous spectrum of genetic susceptibility from monogenic causative variants with complete Mendelian inheritance, over NOD2 variants with moderate penetrance to minute penetrance in most common susceptibility variants predisposing to conventional polygenic IBD. We discuss advances to understand monogenic IBD and review recently identified genetic defects. We describe an integrative model for genetic susceptibility variants of conventional IBD and monogenic IBD-like intestinal inflammation in the context of microbial commensal colonization and infection susceptibility.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Genes / genetics*
  • Genetic Diseases, Inborn / complications*
  • Genetic Diseases, Inborn / genetics
  • Genetic Predisposition to Disease*
  • Humans
  • Inflammatory Bowel Diseases / etiology*