PDF(Pubmed)
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 multicenter 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 1 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.
摘要：
非常早发性炎症性肠病（VEO-IBD）的患者可能由于潜在的单基因先天性免疫错误（IEI）而出现。在种族人群中，单基因IBD的病因存在很大差异。这项多中心研究是对16名伊朗VEO-IBD患者进行的。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。所有患者均行临床全外显子组测序(WES)。16名患者（8名女性和8名男性），中位年龄为43.5个月。症状发作时的中位年龄为4个月。大多数患者（12，75％）有血亲父母。慢性非血性腹泻（13，81.3%）和肛周疾病，包括肛周脓肿（6，37.5%），肛裂（6，37.5%），或肛瘘（2，12.5％）是最常见的表现。WES在13例患者中发现了一系列遗传变异（81.3%）：IL10RB（6，37.5%），MVK（3，18.8%），一名患者的CASP8、SLC35C1、G6PC3和IKBKB，分别。在3例患者（18.7％）中，未发现变异。流式细胞术确定了一系列异常，有助于评估遗传诊断的证据。调查结束时,3例（18.8%）患者死亡。这种具有广谱基因的单基因缺陷的高比率重申了在婴儿发作的IBD患者中研究IEI的重要性。
