Genetic heterogeneity of Mendelian susceptibility to mycobacterial infection
Genetic heterogeneity of Mendelian susceptibility to mycobacterial infection
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DOI：
10.1016/s1286-4579(00)01311-3
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发表时间：
2000-11-01
影响因子：
5.8
通讯作者：
Casanova, JL
中科院分区：
文献类型：
--
作者：
Döffinger, R;Altare, F;Casanova, JL
孟德尔对低毒力分枝杆菌物种（例如卡介苗（BCG）和环境非结核分枝杆菌（NTM））的易感性是一种表型异质综合征。因此，长期以来人们一直怀疑它具有遗传异质性。在过去的 5 年里，这一预测已得到证实，四个基因（IFNGR1、IFNGR2、IL12B、IL12RB1）的不同类型突变（显性或隐性、无功能或功能减退）揭示了等位基因和非等位基因异质性。由这些突变引起的八种疾病在遗传上不同，但在免疫学上相关，因为 IFN-γ 介导的免疫受损是所有患者分枝杆菌感染的常见致病机制。表型的严重程度取决于基因型。与部分 IFN-γ R1 和 IFN-γ R2 缺陷以及完全 IL-12 p40 和 IL-12R beta1 缺陷相比，完全 IFN-γ R1 和 IFN-γ R2 缺陷使患者更容易出现更严重的临床病程。 (C) 2000 年科学与医学版 Elsevier SAS。
Mendelian susceptibility to poorly virulent mycobacterial species, such as bacillus Calmette-Guerin (BCG) and environmental nontuberculous mycobacteria (NTM), is a phenotypically heterogeneous syndrome. It has therefore long been suspected to be genetically heterogeneous. In the past 5 years, this prediction has been confirmed and different types of mutations (dominant or recessive, nonfunctional or hypofunctional) in four genes (IFNGR1, IFNGR2, IL12B, IL12RB1) have revealed both allelic and nonallelic heterogeneity. The eight disorders resulting from these mutations are genetically different but immunologically related, as impaired IFN-gamma -mediated immunity is the common pathogenic mechanism accounting for mycobacterial infection in all patients. The severity of the phenotype depends on the genotype. Complete IFN-gamma R1 and IFN-gamma R2 deficiencies predispose patients to a more severe clinical course than partial IFN-gamma R1 and IFN-gamma R2 deficiencies and complete IL-12 p40 and IL-12R beta1 deficiencies. (C) 2000 Editions scientifiques et medicales Elsevier SAS.