Efficient detection of thirty-seven new IL2RG mutations in human X-linked severe combined immunodeficiency
Efficient detection of thirty-seven new IL2RG mutations in human X-linked severe combined immunodeficiency
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DOI：
10.1006/clim.2000.4846
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发表时间：
2000-04-01
影响因子：
8.6
通讯作者：
Hsu, AP
中科院分区：
文献类型：
--
作者：
Niemela, JE;Puck, JM;Hsu, AP
X连锁严重联合免疫缺陷（XSCID）是一种罕见的和潜在的致命性疾病，由IL 2 RG突变引起，IL 2 RG是编码白细胞介素-2受体γ链的基因，是淋巴细胞发育和功能所必需的多种细胞因子受体的组成部分。迄今为止，已经发表了超过100种不同的IL 2 RG突变导致XSCID。本文报道了37例新发现的IL-2 RG基因突变，其中点突变23例，小缺失10例，单核苷酸插入3例，大缺失1例，复合突变2例。超过一半的突变（37个中的22个）被预测为导致不稳定的IL 2 RG mRNA。其余14个突变破坏了所有细胞因子受体家族成员共有的保守功能基序;改变了蛋白质构象、电荷或疏水性;或改变了蛋白质的细胞内部分，这对于与包括Janus家族酪氨酸激酶3在内的信号转导分子的适当相互作用至关重要。
X-linked severe combined immunodeficiency (XSCID) is a rare and potentially fatal disease caused by mutations of IL2RG, the gene encoding the interleukin-2 receptor gamma chain, a component of multiple cytokine receptors that are essential for lymphocyte development and function. To date, over 100 different mutations of IL2RG resulting in XSCID have been published. Using nonradioactive, direct DNA sequencing of a single PCR amplicon containing the whole IL2RG gene, we found IL2RG mutations in 78 previously unpublished unrelated cases of XSCID, We report 37 newly identified mutations of IL2RG, including 23 point mutations, 10 small deletions, 3 instances of the same single nucleotide insertion, 1 large deletion, and 2 complex mutations. More than half of the mutations (22 of 37) were predicted to result in unstable IL2RG mRNA. The remaining 14 mutations disrupted conserved functional motifs common to all cytokine receptor family members; changed protein conformation, charge, or hydrophobicity; or altered the intracellular portion of the protein, which is critical for proper interaction with signal-transducing molecules including Janus family tyrosine kinase 3.