Molecular characterization of a large cohort of patients with Chronic Granulomatous Disease and identification of novel CYBB mutations: An Italian multicenter study
Molecular characterization of a large cohort of patients with Chronic Granulomatous Disease and identification of novel CYBB mutations: An Italian multicenter study
复制标题
DOI：
10.1016/j.molimm.2009.03.016
复制
发表时间：
2009-06-01
影响因子：
3.6
通讯作者：
Martire, Baldassarre
中科院分区：
文献类型：
--
作者：
Di Matteo, Gigliola;Giordani, Lucia;Martire, Baldassarre
慢性肉芽肿病 (CGD) 是一种罕见的遗传性疾病，由于 NADPH 氧化酶活性缺失，吞噬细胞无法产生抗菌超氧化物。在约 65% 的病例中，该疾病是由于影响 X 连锁 CYBB 基因的突变所致，该基因编码 NADPH 氧化酶的 gp91(phox) 亚基。我们通过 DHPLC 和直接测序研究了 34 名 CGD 男性患者。在 33 名患者的 CYBB 基因中发现突变，其中 9 例为新突变：1 个无义突变 (c.1123 G>T)、3 个错义突变 (c.58G>A; c.1076 G>C; c.1357 T>A)、2 个剪接位点突变 (c.141+5G>T; c.142-1G>A)、1 个重复(c.42-45dupCATT)、1 处缺失 (c.184delT) 和 1 处罕见的两个非连续核苷酸缺失 (c.1287delT+c.1290delC)。一名患者在编码 NADPH 氧化酶 p47(phox) 亚基的 NCF-1 基因的外显子 2 中存在最常见的 GT 纯合缺失。通过分子和 FISH 研究对 23 名患者母亲和 16 名女性亲属进行了携带者分析。无法证明临床症状的严重程度与突变类型之间存在明确的相关性。这项研究进一步支持了该疾病的巨大异质性以及遗传分析是获得 CGD 明确诊断的关键步骤的观点。 (C) 2009 Elsevier Ltd. 保留所有权利。
Chronic Granulomatous Disease (CGD) is a rare inherited disorder in which phagocytes fail to produce antimicrobial superoxide because NADPH oxidase activity is absent. In about 65% of the cases, the disease is due to mutations affecting the X-linked CYBB gene, encoding the gp91(phox) subunit of NADPH oxidase. We investigated 34 CGD male patients by DHPLC and direct sequencing. A mutation was found in the CYBB gene of 33 patients and 9 of these were novel: one non-sense mutation (c.1123 G>T), three missense mutations (c.58G>A; c.1076 G>C; c.1357 T>A), two splice site mutations (c.141+5G>T; c.142-1G>A), one duplication (c.42-45dupCATT), one deletion (c.184delT), and one rare deletion of two non-contiguous nucleotides (c.1287delT+c.1290delC). One patient had the most frequent GT homozygous deletion in exon2 of the NCF-1 gene encoding the p47(phox) subunit of NADPH oxidase. The carrier analysis was performed in 23 patients' mothers and 16 female relatives through molecular and FISH studies. No clear correlation between the severity of clinical symptoms and the type of mutation could be demonstrated. This study further supports the great heterogeneity of the disease and the notion that genetic analysis is a critical step in obtaining a definitive diagnosis for CGD. (C) 2009 Elsevier Ltd. All rights reserved.