Genetic lessons learned from X-linked Mendelian susceptibility to mycobacterial diseases.
Genetic lessons learned from X-linked Mendelian susceptibility to mycobacterial diseases.
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DOI：
10.1111/j.1749-6632.2011.06273.x
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发表时间：
2011-12
影响因子：
5.2
通讯作者：
Casanova JL
中科院分区：
文献类型：
--
作者：
Bustamante J;Picard C;Boisson-Dupuis S;Abel L;Casanova JL
分枝杆菌病孟德尔易感性（MSMD）是一种罕见的综合征，使人易患由弱毒分枝杆菌引起的临床疾病，如牛分枝杆菌卡介苗和非结核性环境分枝杆菌（EM）。自1996年以来，在涉及il -12/23依赖性、IFN-γ介导的免疫的6个常染色体基因中发现了引起msmd的突变。这篇综述的目的是提供描述的两种形式的x连锁隐性（XR） MSMD。人们早就知道，NEMO和CYBB这两个基因的种系突变会导致其他人类疾病——色素失禁（IP）和无汗液性外胚层发育不良伴免疫缺陷（EDA-ID） （NEMO/IKKG），以及x连锁慢性肉芽肿病（CGD） （CYBB）——但这两个基因中的任何一个的特异性突变最近被证明会导致XR-MSMD。NEMO是几种NF-κ b依赖性信号通路的重要组成部分。NEMO中引起msmd的突变选择性地影响单核细胞中依赖cd40的IL-12诱导。CYBB编码gp91phox，这是吞噬细胞中NADPH氧化酶的重要组成部分。引起msmd的CYBB突变选择性地影响巨噬细胞的呼吸爆发。因此，NEMO和CYBB的突变可能通过选择性地对单一信号通路（CD40-IL-12， NEMO）或单一细胞类型（巨噬细胞，CYBB）施加有害影响而导致MSMD。这些实验说明了多效性基因中的特定种系突变如何分离信号通路或细胞系，从而导致令人惊讶的狭窄临床表型。
Mendelian susceptibility to mycobacterial disease (MSMD) is a rare syndrome conferring predisposition to clinical disease caused by weakly virulent mycobacteria, such as Mycobacterium bovis Bacille Calmette Guérin (BCG) vaccines and nontuberculous, environmental mycobacteria (EM). Since 1996, MSMD-causing mutations have been found in six autosomal genes involved in IL-12/23-dependent, IFN-γ-mediated immunity. The aim of this review is to provide the description of the two described forms of X-linked recessive (XR) MSMD. Germline mutations in two genes, NEMO and CYBB, have long been known to cause other human diseases—incontinentia pigmenti (IP) and anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (NEMO/IKKG), and X-linked chronic granulomatous disease (CGD) (CYBB)—but specific mutations in either of these two genes have recently been shown to cause XR-MSMD. NEMO is an essential component of several NF-κB-dependent signaling pathways. The MSMD-causing mutations in NEMO selectively affect the CD40-dependent induction of IL-12 in mononuclear cells. CYBB encoded for gp91phox, which is an essential component of the NADPH oxidase in phagocytes. The MSMD-causing mutation in CYBB selectively affects the respiratory burst in macrophages. Mutations in NEMO and CYBB may therefore cause MSMD by selectively exerting their deleterious impact on a single signaling pathway (CD40–IL-12, NEMO) or a single cell type (macrophages, CYBB). These experiments illustrate how specific germline mutations in pleiotropic genes can dissociate signalling pathways or cell lineages, thereby resulting in surprisingly narrow clinical phenotypes.
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影响因子：
5.1
作者：
Camcioglu, Y;Picard, C;Casanova, JL
通讯作者：
Casanova, JL
影响因子：
4.4
作者：
Chapgier, Ariane;Wynn, Robert F.;Arkwright, Peter D.
通讯作者：
Arkwright, Peter D.
影响因子：
3.7
作者：
Boisson-Dupuis, Stephanie;El Baghdadi, Jamila;Casanova, Jean-Laurent
通讯作者：
Casanova, Jean-Laurent
影响因子：
9.8
作者：
Aradhya, S;Courtois, G;Nelson, DL
通讯作者：
Nelson, DL
影响因子：
11.8
作者：
de Moraes-Vasconcelos, D;Grumach, AS;Duarte, AJS
通讯作者：
Duarte, AJS