Genomic Testing Identifies Monogenic Causes in Patients with Very Early-Onset Inflammatory Bowel Disease: A Multi-center Survey in an Iranian Cohort.

IF 3.4 3区医学 Q3 IMMUNOLOGY

Clinical and experimental immunology Pub Date : 2024-04-23 DOI:10.1093/cei/uxae037

Golnaz Eslamian, M. Jamee, Tooba Momen, P. Rohani, Sarehossadat Ebrahimi, M. Mesdaghi, Soodeh Ghadimi, M. Mansouri, S. Mahdaviani, M. Sadeghi-shabestari, M. Fallahpour, B. Shamsian, N. Eslami, S. Sharafian, N. Dara, Peiman Nasri, N. Amini, Javad Enayat, Mazdak Fallahi, Leila Ghasemi Hashtrodi, Mohammad Shojaei, Martha Guevara Becerra, H. Uhlig, Z. Chavoshzadeh

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引用次数: 0

Abstract

Patients with very early-onset inflammatory bowel disease (VEO-IBD) may present because of underlying monogenic inborn errors of immunity (IEI). Strong differences have been observed in the causes of monogenic IBD among ethnic populations. This multi-center study was carried out on 16 Iranian patients with VEO-IBD. We reviewed clinical and basic immunologic evaluation including flow cytometry and immunoglobulin levels. All patients underwent clinical whole exome sequencing (WES). Sixteen patients (8 females and 8 males) with a median age of 43.5 months were enrolled. The median age at the onset of symptoms was 4 months. Most patients (12, 75%) had consanguineous parents. Chronic non-bloody diarrhea (13, 81.3%) and perianal diseases including perianal abscess (6, 37.5%), anal fissure (6, 37.5%), or anal fistula (2, 12.5%) were the most common manifestations. WES identified a spectrum of genetic variants in 13 patients (81.3%): IL10RB (6, 37.5%), MVK (3, 18.8%), and CASP8, SLC35C1, G6PC3, and IKBKB in one patient, respectively. In 3 patients (18.7%) no variant was identified. Flow cytometry identified a spectrum of abnormalities that helped to assess the evidence of genetic diagnosis. At the end of the survey, 3 (18.8%) patients were deceased. This high rate of monogenic defects with a broad spectrum of genes reiterates the importance of investigating IEI in patients with infantile-onset IBD.

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基因组检测发现极早期炎症性肠病患者的单基因病因：伊朗队列中的多中心调查

极早发炎症性肠病（VEO-IBD）患者可能因潜在的单基因先天性免疫错误（IEI）而发病。据观察，不同种族人群的单基因 IBD 病因存在很大差异。这项多中心研究针对 16 名伊朗 VEO-IBD 患者展开。我们回顾了临床和基础免疫学评估，包括流式细胞术和免疫球蛋白水平。所有患者都进行了临床全外显子组测序（WES）。16名患者（8女8男）的中位年龄为43.5个月。发病时的中位年龄为 4 个月。大多数患者（12 人，75%）的父母是近亲。慢性非血性腹泻（13 例，81.3%）和肛周疾病（包括肛周脓肿（6 例，37.5%）、肛裂（6 例，37.5%）或肛瘘（2 例，12.5%））是最常见的表现。WES 在 13 名患者（81.3%）中发现了一系列基因变异：IL10RB（6 例，占 37.5%）、MVK（3 例，占 18.8%），以及 CASP8、SLC35C1、G6PC3 和 IKBKB（1 例）。3名患者（18.7%）未发现变异。流式细胞术发现了一系列异常，有助于评估基因诊断的证据。调查结束时，3 名患者（18.8%）已经死亡。这种具有广泛基因谱的单基因缺陷率很高，这重申了在婴儿期发病的 IBD 患者中调查 IEI 的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical and experimental immunology 医学-免疫学

CiteScore

8.40

自引率

2.20%

发文量

101

审稿时长

3-8 weeks

期刊介绍： Clinical & Experimental Immunology (established in 1966) is an authoritative international journal publishing high-quality research studies in translational and clinical immunology that have the potential to transform our understanding of the immunopathology of human disease and/or change clinical practice. The journal is focused on translational and clinical immunology and is among the foremost journals in this field, attracting high-quality papers from across the world. Translation is viewed as a process of applying ideas, insights and discoveries generated through scientific studies to the treatment, prevention or diagnosis of human disease. Clinical immunology has evolved as a field to encompass the application of state-of-the-art technologies such as next-generation sequencing, metagenomics and high-dimensional phenotyping to understand mechanisms that govern the outcomes of clinical trials.