Pathophysiology and Immunology Department, Hanoi Medical University, 1 - Ton That Tung str., Dongda, Hanoi, Viet Nam; Hematology Department, Vietnam National Hospital of Pediatrics, 18/879 La Thanh str., Dongda, Hanoi, Viet Nam.
Institute of Genome Research, Vietnam Academy of Science and Technology, 18 - Hoang Quoc Viet str., Caugiay, Hanoi, Viet Nam.
Clin Chim Acta. 2022 Aug 1;533:114-121. doi: 10.1016/j.cca.2022.06.003. Epub 2022 Jun 18.
Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder (PID) due to genetic defects in the NADPH oxidase of phagocytes. Affected patients become susceptible to infections such as pneumonia, diarrhea, and skin ulcer types. The patients require life-long treatment with prophylactic antibiotics, antifungals, or hematopoietic stem cell transplantation (HSCT) therapy. Early, accurate diagnosis will contribute to the life-prolonging of patients with CGD. This study's aim is to identify the mutation related to the disease.
Six patients from different Vietnamese families were collected for genetic analysis at Allergy, Immunology, and Rheumatology Department, Vietnam National Hospital Pediatrics. They were diagnosed with CGD by flow cytometry test with the conversion of dihydrorhodamine (DHR) 123 to rhodamine 123.
We performed whole exome sequencing (WES) as a tool for detecting novel mutations. The mutations were confirmed by the Sanger sequencing method in patients and their families. The influence of the mutations was predicted with the in silico analysis tools: PROVEAN, SIFT, PolyPhen 2, Mutation Taster, and MaxEntScan.
In this study, five mutations were found in six unrelated patients with CGD from different Vietnamese families. Three novel pathogenic mutations were detected including one mutation (c.45+2 T>G) in the CYBB gene and two mutations (c.187_188insA and c.289G>C) in the NCF2 gene.
Our results of CGD-related mutations contribute to the general understanding of the etiology of the disease and emphasize that WES sequencing can be used as a tool to help to diagnose carriers as well as assist in genetic counseling and prenatal screening.
慢性肉芽肿病（CGD）是一种罕见的原发性免疫缺陷病（PID），由于吞噬细胞中 NADPH 氧化酶的遗传缺陷所致。受影响的患者易感染肺炎、腹泻和皮肤溃疡等类型。患者需要终身接受预防性抗生素、抗真菌药或造血干细胞移植（HSCT）治疗。早期、准确的诊断将有助于延长 CGD 患者的生命。本研究旨在确定与疾病相关的突变。
来自不同越南家庭的六名患者在越南国家儿童医院过敏、免疫和风湿病科接受了遗传分析。他们通过二氢罗丹明 123（DHR）转化为罗丹明 123的流式细胞术检测被诊断为 CGD。
我们使用全外显子组测序（WES）作为检测新突变的工具。在患者及其家属中，通过 Sanger 测序法确认突变。使用 PROVEAN、SIFT、PolyPhen 2、Mutation Taster 和 MaxEntScan 等计算机分析工具预测突变的影响。
在这项研究中，从不同的越南家庭中发现了六个不相关的 CGD 患者中的五个突变。在六个不相关的 CGD 患者中发现了五个突变，包括一个在 CYBB 基因中的突变（c.45+2T>G）和两个在 NCF2 基因中的突变（c.187_188insA 和 c.289G>C）。
我们对 CGD 相关突变的研究结果有助于全面了解疾病的病因，并强调 WES 测序可用作帮助诊断携带者以及进行遗传咨询和产前筛查的工具。
