Chromosomal Numerical Aberrations and Rare Copy Number Variation in Patients with Inflammatory Bowel Disease.
Chromosomal Numerical Aberrations and Rare Copy Number Variation in Patients with Inflammatory Bowel Disease.
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炎症性肠病患者的染色体数值畸变和罕见的拷贝数变化。
DOI：
10.1093/ecco-jcc/jjac103
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发表时间：
2023-01-27
期刊：
影响因子：
--
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中科院分区：
文献类型：
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作者：
炎症性肠病[IBD]具有复杂的多基因病因。罕见的基因变异可引起单基因肠道炎症。染色体畸变和大结构异常对 IBD 易感性的影响尚不清楚。我们的目的是全面描述具有罕见数量和结构染色体异常的 IBD 患者的表型和患病率。我们对 PubMed 和 Embase 数据库进行了系统的文献检索；并分析了 gnomAD、Clinvar、100 000 Genomes Project 和 DECIPHER 数据库。此外，我们分析了国际儿科 IBD 队列，以研究 IL2RA 重复在 IBD 易感性中的作用。一项荟萃分析表明，X 单体 [特纳综合征] 与 IBD 表达增加相关，超过人群基线（1.86%，95% 置信区间 [CI] 1.48 至 2.34%），并导致 IBD 发病年龄更年轻。几乎没有证据表明克兰费尔特综合征、21 三体、18 三体、马赛克三体 9 和 16 或部分三体会导致 IBD 易感性。拷贝数分析研究表明结果不一致。 X连锁或单倍体不足基因的单等位基因丢失分别通过半合子或杂合子缺失与IBD相关。然而，在健康参考人群中检测到单倍体基因缺失不足，这表明 IBD 的表达能力可能被高估了。先前已确定可能导致 IBD 风险的一项重复涉及 IL2RA/IL15R 基因座。在这里，我们提供了额外的证据，通过在不同的亲属中识别出第二个病例，表明该基因座的微重复可能导致极早发的 IBD。然而，这种遗传畸变中肠道炎症的外显率较低[<2.6%]。特纳综合征与肠道炎症易感性增加有关。 IL2RA/IL15R 基因座的重复可能会增加疾病风险。
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. 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. 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%]. Turner syndrome is associated with increased susceptibility to intestinal inflammation. Duplication of the IL2RA/IL15R loci may contribute to disease risk.
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DOI：
10.1016/j.jaci.2017.10.041
发表时间：
2018-03
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Barzaghi F;Amaya Hernandez LC;Neven B;Ricci S;Kucuk ZY;Bleesing JJ;Nademi Z;Slatter MA;Ulloa ER;Shcherbina A;Roppelt A;Worth A;Silva J;Aiuti A;Murguia-Favela L;Speckmann C;Carneiro-Sampaio M;Fernandes JF;Baris S;Ozen A;Karakoc-Aydiner E;Kiykim A;Schulz A;Steinmann S;Notarangelo LD;Gambineri E;Lionetti P;Shearer WT;Forbes LR;Martinez C;Moshous D;Blanche S;Fisher A;Ruemmele FM;Tissandier C;Ouachee-Chardin M;Rieux-Laucat F;Cavazzana M;Qasim W;Lucarelli B;Albert MH;Kobayashi I;Alonso L;Diaz De Heredia C;Kanegane H;Lawitschka A;Seo JJ;Gonzalez-Vicent M;Diaz MA;Goyal RK;Sauer MG;Yesilipek A;Kim M;Yilmaz-Demirdag Y;Bhatia M;Khlevner J;Richmond Padilla EJ;Martino S;Montin D;Neth O;Molinos-Quintana A;Valverde-Fernandez J;Broides A;Pinsk V;Ballauf A;Haerynck F;Bordon V;Dhooge C;Garcia-Lloret ML;Bredius RG;Kałwak K;Haddad E;Seidel MG;Duckers G;Pai SY;Dvorak CC;Ehl S;Locatelli F;Goldman F;Gennery AR;Cowan MJ;Roncarolo MG;Bacchetta R;Primary Immune Deficiency Treatment Consortium (PIDTC) and the Inborn Errors Working Party (IEWP) of the European Society for Blood and Marrow Transplantation (EBMT)
通讯作者：
Primary Immune Deficiency Treatment Consortium (PIDTC) and the Inborn Errors Working Party (IEWP) of the European Society for Blood and Marrow Transplantation (EBMT)
影响因子：
12.8
作者：
Bakalov VK;Gutin L;Cheng CM;Zhou J;Sheth P;Shah K;Arepalli S;Vanderhoof V;Nelson LM;Bondy CA
通讯作者：
Bondy CA
影响因子：
2
作者：
Hanew, Kunihiko;Tanaka, Toshiaki;Yokoya, Susumu
通讯作者：
Yokoya, Susumu
影响因子：
1.7
作者：
Cox, Devin M.;Butler, Merlin G.
通讯作者：
Butler, Merlin G.
影响因子：
5.2
作者：
Goldacre, Michael J.;Seminog, Olena O.
通讯作者：
Seminog, Olena O.