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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2015; 21(43): 12296-12310
Published online Nov 21, 2015. doi: 10.3748/wjg.v21.i43.12296
Genetics of inflammatory bowel disease from multifactorial to monogenic forms
Anna Monica Bianco, Martina Girardelli, Alberto Tommasini
Anna Monica Bianco, Martina Girardelli, Alberto Tommasini, Institute for Maternal and Child Health-IRCCS “Burlo Garofolo”, 34137 Trieste, Italy
Author contributions: Bianco AM, Girardelli M and Tommasini A contributed equally to writing, editing and revising critically this manuscript.
Supported by grants from the Institute for Maternal and Child Health IRCCS “Burlo Garofolo”, Italy (RC 22/2012).
Conflict-of-interest statement: Bianco AM, Girardelli M and Tommasini A have no conflict of interest to disclose.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Anna Monica Bianco, PhD, Institute for Maternal and Child Health-IRCCS “Burlo Garofolo”, Via dell’Istria, 65/1, 34137 Trieste, Italy.
Telephone: +39-403-785422 Fax: +39-403-785540
Received: April 29, 2015
Peer-review started: May 7, 2015
First decision: July 20, 2015
Revised: August 13, 2015
Accepted: October 23, 2015
Article in press: October 26, 2015
Published online: November 21, 2015

Inflammatory bowel disease (IBD) is a group of chronic multifactorial disorders. According to a recent study, the number of IBD association loci is increased to 201, of which 37 and 27 loci contribute specifically to the development of Crohn’s disease and ulcerative colitis respectively. Some IBD associated genes are involved in innate immunity, in the autophagy and in the inflammatory response such as NOD2, ATG16L1 and IL23R, while other are implicated in immune mediated disease (STAT3) and in susceptibility to mycobacterium infection (IL12B). In case of early onset of IBD (VEO-IBD) within the 6th year of age, the disease may be caused by mutations in genes responsible for severe monogenic disorders such as the primary immunodeficiency diseases. In this review we discuss how these monogenic disorders through different immune mechanisms can similarly be responsible of VEO-IBD phenotype. Moreover we would highlight how the identification of pathogenic genes by Next Generation Sequencing technologies can allow to obtain a rapid diagnosis and to apply specific therapies.

Keywords: Inflammatory bowel disease, Primary immunodeficiency disease, Early onset, Next generation sequencing, Genome wide association studies

Core tip: Genetic investigation is of fundamental importance describing inflammatory bowel disease (IBD) as a complex disease, as well as in identifying the monogenic disorders that may present with IBD-like features. Using third-generation technology should be leveraged to accelerate the screening and allow the identification of the most rare monogenic defects. Furthermore, the study of genetic variants in monogenic and in sporadic IBD could help unraveling the complex interplay between defective and compensatory immune responses, opening the way to the identification of new targets for therapy.