Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Hum Mutat. 2017 Oct;38(10):1286-1296. doi: 10.1002/humu.23302. Epub 2017 Aug 3.
IFN-γ signaling is essential for the innate immune defense against mycobacterial infections. IFN-γ signals through the IFN-γ receptor, which consists of a tetramer of two IFN-γR1 chains in complex with two IFN-γR2 chains, where IFN-γR1 is the ligand-binding chain of the interferon-γ receptor and IFN-γR2 is the signal-transducing chain of the IFN-γ receptor. Germline mutations in the gene IFNGR1 encoding the IFN-γR1 cause a primary immunodeficiency that mainly leads to mycobacterial infections. Here, we review the molecular basis of this immunodeficiency in the 130 individuals described to date, and report mutations in five new individuals, bringing the total number to 135 individuals from 98 kindreds. Forty unique IFNGR1 mutations have been reported and they exert either an autosomal dominant or an autosomal recessive effect. Mutations resulting in premature stopcodons represent the majority of IFNGR1 mutations (60%; 24 out of 40), followed by amino acid substitutions (28%, 11 out of 40). All known mutations, as well as 287 other variations, have been deposited in the online IFNGR1 variation database (www.LOVD.nl/IFNGR1). In this article, we review the function of IFN-γR1 and molecular genetics of human IFNGR1.
IFN-γ 信号对于抵抗分枝杆菌感染的固有免疫防御至关重要。IFN-γ 通过 IFN-γ 受体信号转导，IFN-γ 受体由两个 IFN-γR1 链组成的四聚体与两个 IFN-γR2 链组成，其中 IFN-γR1 是干扰素-γ 受体的配体结合链，IFN-γR2 是 IFN-γ 受体的信号转导链。编码 IFN-γR1 的 IFNGR1 基因的种系突变导致原发性免疫缺陷，主要导致分枝杆菌感染。在这里，我们回顾了迄今为止描述的 130 个人中的这种免疫缺陷的分子基础，并报告了 5 个新个体的突变，使总数达到 98 个家系中的 135 个个体。已经报道了 40 个独特的 IFNGR1 突变，它们具有常染色体显性或常染色体隐性作用。导致提前终止密码子的突变代表了 IFNGR1 突变的大多数（60%；40 个中的 24 个），其次是氨基酸取代（28%，40 个中的 11 个）。所有已知的突变以及 287 个其他变异都已被存入在线 IFNGR1 变异数据库（www.LOVD.nl/IFNGR1）。在本文中，我们回顾了 IFN-γR1 的功能和人类 IFNGR1 的分子遗传学。
