A novel point mutation in the CYBB gene promoter leading to a rare X minus chronic granulomatous disease variant-Impact on the microbicidal activity of neutrophils
A novel point mutation in the CYBB gene promoter leading to a rare X minus chronic granulomatous disease variant-Impact on the microbicidal activity of neutrophils
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DOI：
10.1016/j.bbadis.2009.01.005
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发表时间：
2009-03-01
影响因子：
6.2
通讯作者：
Stasia, Marie Jose
中科院分区：
文献类型：
--
作者：
Defendi, Federica;Decleva, Eva;Stasia, Marie Jose
本文报告了一个意大利家族中的一个非典型和极其罕见的X连锁CGD病例，其特征是gp 91 phox（X91（-）CGD）的低表达。CYBB基因启动子中的一种新的点突变（在-54 T至-56 T位置插入T）似乎阻止了该基因在患者嗜中性粒细胞中的完全表达，并与整个细胞群中的残留氧化酶活性相关。嗜酸性粒细胞中氧化酶的表达和功能活性似乎几乎正常。凝胶位移分析表明，突变导致减少与DNA结合蛋白的相互作用。患者粒细胞中的总O-2（-）产生量（正常值的5-7%）在与S接触45分钟和60分钟后不支持杀微生物能力。金黄色葡萄球菌和C.白色念珠菌。尽管有这种残留的氧化酶活性，患者仍遭受严重和危及生命的感染。得出结论，在这些X91（-）CGD中性粒细胞。O-2（-）产生本身不足以保护患者免受严重感染。(C)2009爱思唯尔有限公司版权所有。
This article reports an atypical and extremely rare case of X-linked CGD in an Italian family characterized by a low expression of gp91 phox (X91(-) CGD). A novel point mutation in the CYBB gene's promoter (insertion of a T at position -54T to -56T) appeared to prevent the full expression of this gene in the patient's neutrophils and correlated with a residual oxidase activity in the whole cells population. The expression and functional activity of the oxidase in eosinophils appeared to be almost normal. Gel shift assays indicated that the mutation led to decreased interactions with DNA-binding proteins. The total O-2(-) production in the patient's granulocytes (5-7% of normal) supported no microbicidal power after 45 min and 60 min of contact with S. aureus and C. albicans, respectively. Despite this residual oxidase activity, the patients suffered from severe and life-threatening infections. It was concluded that in these X91(-) CGD neutrophils. the O-2(-) production per se was not sufficient to protect the patient against severe infections. (C) 2009 Elsevier B.V. All rights reserved.