Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.
Scand J Immunol. 2019 Jul;90(1):e12767. doi: 10.1111/sji.12767. Epub 2019 Apr 25.
One of the components of NADPH oxidase is p47-phox, encoded by NCF1 gene. This study aims to find new genetic changes and clinical features in 38 Iranian patients with autosomal recessive chronic granulomatous disease (AR-CGD) caused by NCF1 gene defect. Patients who had abnormal NBT and DHR-1,2,3 assay with loss of p47-phox in Western blotting were included in this study. After recording demographic and clinical data, PCR amplification was performed followed by direct sequencing for all exons and exon-intron boundaries. The most common form of CGD in Iran was AR-CGD due to consanguinity marriages. Among patients with AR-CGD, NCF1 deficiency was found to be more common than other forms. Cutaneous involvements (53%), pulmonary infections (50%) and lymphadenopathy (29%) were more prevalent than other clinical manifestations of CGD. Mutation analysis of NCF1 gene identified five different mutations. Homozygous delta GT deletion (c.75_76delGT) was the most frequent mutation and was detected in more than 63% of families. Six families had a nonsense mutation in exon 7 (c.579G > A). Two novel mutations were found in exon 4 in two families, including a missense mutation (c.328C > T) and a nine-nucleotide deletion (c.331_339delTGTCCCCAC). Genetic detection of these mutations may result in early diagnosis and prevention of possible complications of the disease. This could be useful for timely decision-making for haematopoietic stem cell transplantation and for carrier detection as well as prenatal diagnosis of next children in the affected families. Our findings might help to predict outcomes, raise awareness and help effective treatment in these patients.
NADPH 氧化酶的一个组成部分是 p47-phox，由 NCF1 基因编码。本研究旨在发现 38 例伊朗常染色体隐性慢性肉芽肿病（AR-CGD）患者新的遗传变化和临床特征，这些患者因 NCF1 基因缺陷导致 NADPH 氧化酶功能异常。本研究纳入了 NBT 和 DHR-1,2,3 检测异常，Western blot 检测 p47-phox 丢失的患者。记录人口统计学和临床数据后，对所有外显子和外显子-内含子边界进行 PCR 扩增和直接测序。伊朗最常见的 CGD 形式是由近亲结婚引起的 AR-CGD。在 AR-CGD 患者中，NCF1 缺乏比其他形式更常见。皮肤受累（53%）、肺部感染（50%）和淋巴结病（29%）比 CGD 的其他临床表现更为常见。NCF1 基因突变分析发现了五种不同的突变。纯合 delta GT 缺失（c.75_76delGT）是最常见的突变，在超过 63%的家庭中发现。六个家庭在外显子 7 中存在无义突变（c.579G>A）。两个新的突变在两个家庭的外显子 4 中发现，包括错义突变（c.328C>T）和 9 个核苷酸缺失（c.331_339delTGTCCCCAC）。这些突变的遗传检测可能导致早期诊断和预防疾病的并发症。这对于及时决定进行造血干细胞移植、携带者检测以及受影响家庭中下一胎的产前诊断可能是有用的。我们的发现可能有助于预测这些患者的结局，提高认识并帮助进行有效的治疗。
