Journal article
Chromosomal numeric aberrations and rare copy number variation in patients with inflammatory bowel disease
- Abstract:
-
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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Files:
-
-
(Preview, Version of record, pdf, 2.2MB, Terms of use)
-
- Publisher copy:
- 10.1093/ecco-jcc/jjac103
- Publisher:
- Oxford University Press
- Journal:
- Journal of Crohn's and Colitis More from this journal
- Volume:
- 17
- Issue:
- 1
- Pages:
- 49–60
- Publication date:
- 2022-07-30
- Acceptance date:
- 2022-07-20
- DOI:
- EISSN:
-
1876-4479
- ISSN:
-
1873-9946
- Pmid:
-
35907265
- Language:
-
English
- Keywords:
- Pubs id:
-
1272663
- Local pid:
-
pubs:1272663
- Deposit date:
-
2022-08-26
Terms of use
- Copyright holder:
- Dirvanskyte et al.
- Copyright date:
- 2022
- Rights statement:
- © The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
If you are the owner of this record, you can report an update to it here: Report update to this record