Browse by author
Lookup NU author(s): Dr Helen GriffinORCiD, Professor Sophie Hambleton
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2022 The Author(s). Published by Oxford University Press on behalf of European Crohn's and Colitis Organisation. Background and Aims: Inflammatory bowel diseases [IBD] have a complex polygenic aetiology. Rare genetic variants can cause monogenic intestinal inflammation. The impact of chromosomal aberrations and large structural abnormalities on IBD susceptibility is not clear. We aimed to comprehensively characterise the phenotype and prevalence of patients with IBD who possess rare numerical and structural chromosomal abnormalities. Methods: We performed a systematic literature search of databases PubMed and Embase; and analysed gnomAD, Clinvar, the 100 000 Genomes Project, and DECIPHER databases. Further, we analysed international paediatric IBD cohorts to investigate the role of IL2RA duplications in IBD susceptibility. Results: A meta-analysis suggests that monosomy X [Turner syndrome] is associated with increased expressivity of IBD that exceeds the population baseline (1.86%, 95% confidence interval [CI] 1.48 to 2.34%) and causes a younger age of IBD onset. There is little evidence that Klinefelter syndrome, Trisomy 21, Trisomy 18, mosaic Trisomy 9 and 16, or partial trisomies contribute to IBD susceptibility. Copy number analysis studies suggest inconsistent results. Monoallelic loss of X-linked or haploinsufficient genes is associated with IBD by hemizygous or heterozygous deletions, respectively. However, haploinsufficient gene deletions are detected in healthy reference populations, suggesting that the expressivity of IBD might be overestimated. One duplication that has previously been identified as potentially contributing to IBD risk involves the IL2RA/IL15R loci. Here we provide additional evidence that a microduplication of this locus may predispose to very-early-onset IBD by identifying a second case in a distinct kindred. However, the penetrance of intestinal inflammation in this genetic aberration is low [<2.6%]. Conclusions: Turner syndrome is associated with increased susceptibility to intestinal inflammation. Duplication of the IL2RA/IL15R loci may contribute to disease risk.
Author(s): Dirvanskyte P, Gurram B, Bolton C, Warner N, Jones KDJ, Griffin HR, Park JY, Keller K-M, Gilmour KC, Hambleton S, Muise AM, Wysocki C, Uhlig HH
Publication type: Article
Publication status: Published
Journal: Journal of Crohn's and Colitis
Year: 2023
Volume: 17
Issue: 1
Pages: 49-60
Online publication date: 30/07/2022
Acceptance date: 02/04/2018
Date deposited: 31/05/2023
ISSN (print): 1873-9946
ISSN (electronic): 1876-4479
Publisher: Oxford University Press
URL: https://doi.org/10.1093/ecco-jcc/jjac103
DOI: 10.1093/ecco-jcc/jjac103
Data Access Statement: All data described are available in deposited databases [such as Decipher or GEL] or are available on request.
PubMed id: 35907265
Altmetrics provided by Altmetric
