ABSTRACT

We describe a cohort of 25 Iranian patients with infantile inflammatory bowel disease (IBD), 14 (56%) of whom had monogenic defects. After proper screening, patients were referred for whole exome sequencing (WES). Four patients had missense mutations in the IL10 RA, and one had a large deletion in the IL10 RB. Four patients had mutations in genes implicated in host:microbiome homeostasis, including TTC7A deficiency, and two patients with novel mutations in the TTC37 and NOX1. We found a novel homozygous mutation in the SRP54 in a deceased patient and the heterozygous variant in his sibling with a milder phenotype. Three patients had combined immunodeficiency: one with ZAP-70 deficiency (T⁺B⁺NK⁻), and two with atypical SCID due to mutations in RAG1 and LIG4. One patient had a G6PC3 mutation without neutropenia. Eleven of the 14 patients with monogenic defects were results of consanguinity and only 4 of them were alive to this date.

摘要

我们描述了 25 名患有婴儿炎症性肠病 (IBD) 的伊朗患者，其中 14 名 (56%) 患有单基因缺陷。经过适当的筛选后，患者被转诊进行全外显子组测序（WES）。4 名患者在IL10 RA 中有错义突变，1 名在IL10 RB 中有大的缺失。四名患者在与宿主微生物组稳态有关的基因中发生突变，包括TTC7A缺乏症，以及两名患者在TTC37和NOX1 中发生新突变。我们在SRP54 中发现了一个新的纯合突变在一名已故患者和他兄弟姐妹中的杂合变异体中，表型较轻。三名患者患有联合免疫缺陷：一名患有 ZAP-70 缺陷（T ⁺ B ⁺ NK ^-），两名患有由于RAG1和LIG4突变导致的非典型 SCID 。一名患者有G6PC3突变，但没有中性粒细胞减少症。14 名具有单基因缺陷的患者中有 11 名是近亲导致的，其中只有 4 名至今还活着。