Abstract：
BACKGROUND: Infantile-onset inflammatory bowel disease (IOIBD) is a gastrointestinal inflammatory condition often associated with monogenic disorders and is frequently caused by Interleukin-10 deficiencies. This study aimed to identify the mutation responsible for IBD in an 8-year-old patient from an Iranian family with consanguineous parents.
METHODS: Whole-exome sequencing (WES) was employed to identify disease-causing variations. Furthermore, we utilized integrated experimental data of HADDOCK molecular docking platform, including NMR spectroscopy, to characterize the mutant protein and elucidate the underlying functional mechanism of the identified mutation\'s pathogenicity.
RESULTS: Our findings revealed a novel 19-bp deletion mutation (c.25_43del, p.Leu9CysfsTer15) in the IL10RB gene. Sanger sequencing confirmed that this variant was inherited in homozygous state within this family, marking the first mutation identified in exon 1 of this gene. Molecular docking simulation demonstrated that the mutant form of IL10RB exhibited reduced affinity for binding to the Interleukin-10 ligand, leading to disruptions in downstream cellular signaling pathways.
CONCLUSIONS: The identification of this novel genetic variant as a causative factor for IOIBD highlights the clinical value of utilizing genetic testing, such as WES, as a reliable diagnostic approach for patients affected by this condition.
METHODS: Whole-exome sequencing (WES) was employed to identify disease-causing variations. Furthermore, we utilized integrated experimental data of HADDOCK molecular docking platform, including NMR spectroscopy, to characterize the mutant protein and elucidate the underlying functional mechanism of the identified mutation\'s pathogenicity.
RESULTS: Our findings revealed a novel 19-bp deletion mutation (c.25_43del, p.Leu9CysfsTer15) in the IL10RB gene. Sanger sequencing confirmed that this variant was inherited in homozygous state within this family, marking the first mutation identified in exon 1 of this gene. Molecular docking simulation demonstrated that the mutant form of IL10RB exhibited reduced affinity for binding to the Interleukin-10 ligand, leading to disruptions in downstream cellular signaling pathways.
CONCLUSIONS: The identification of this novel genetic variant as a causative factor for IOIBD highlights the clinical value of utilizing genetic testing, such as WES, as a reliable diagnostic approach for patients affected by this condition.
摘要：
背景：婴儿发作性炎症性肠病（IOIBD）是一种胃肠道炎症性疾病，通常与单基因疾病相关，通常由白细胞介素10缺乏引起。这项研究旨在鉴定来自伊朗家庭的8岁患者与近亲父母的IBD突变。
方法：采用全外显子组测序（WES）来鉴定致病变异。此外，我们利用HADDOCK分子对接平台的综合实验数据，包括核磁共振波谱,表征突变蛋白并阐明鉴定的突变致病性的潜在功能机制。
结果：我们的发现揭示了一个新的19bp缺失突变（c.25_43del，p.Leu9CysfsTer15)在IL10RB基因中。Sanger测序证实，该变体在该家族中以纯合状态遗传，标记该基因外显子1中鉴定的第一个突变。分子对接模拟表明，IL10RB的突变形式表现出与白细胞介素-10配体结合的亲和力降低，导致下游细胞信号通路中断。
结论：将这种新的遗传变异确定为IOIBD的致病因素突出了利用基因检测的临床价值，如WES，作为受这种情况影响的患者的可靠诊断方法。
方法：采用全外显子组测序（WES）来鉴定致病变异。此外，我们利用HADDOCK分子对接平台的综合实验数据，包括核磁共振波谱,表征突变蛋白并阐明鉴定的突变致病性的潜在功能机制。
结果：我们的发现揭示了一个新的19bp缺失突变（c.25_43del，p.Leu9CysfsTer15)在IL10RB基因中。Sanger测序证实，该变体在该家族中以纯合状态遗传，标记该基因外显子1中鉴定的第一个突变。分子对接模拟表明，IL10RB的突变形式表现出与白细胞介素-10配体结合的亲和力降低，导致下游细胞信号通路中断。
结论：将这种新的遗传变异确定为IOIBD的致病因素突出了利用基因检测的临床价值，如WES，作为受这种情况影响的患者的可靠诊断方法。
