The causative genes and biological structure analyses of primary immunodeficiencies.

原发性免疫缺陷的致病基因和生物结构分析。

基本信息

批准号：
09470180
负责人：
KONDO Naomi
金额：
$ 7.17万
依托单位：
Gifu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470180/
关键词：
IgGィイD22ィエD2 deficiency CVID Ataxia-telangiectasia Membrane-bound Cγ2 BLM ATM Bloom症候群

项目摘要

The causative genes of several primary immunodeficiencies were found and structurally analyzed.(1) The causative gene of selective IgGィイD22ィエD2 deficiency was identified, and was recognized by the expression experiment. We sequenced the Cγ2 gene region, and in both patients a homozygous one-base insertion (1793insG) was present in exon 4 of the Cγ2 gene, just upstream from the alternative splice site for M exons. The mutant membrane-bound γ2 heavy chain loses the transmembrane domain and the evolutionarily conserved cytoplasmic domain. Considering several lines of evidence showing that intact expression of the membrane-bound heavy chain is essential for a normal response of B cells and production of secreted immunoglobulin in mice, we concluded that 1793insG is responsible for selective and complete IgGィイD22ィエD2 deficiency in these two siblings. This is the first documentation of a mutation in human selective IgGィイD22ィエD2 deficiency. (J. Clin Invest. 1998. 101 : 677-681.)(2) The causative genes of Bloom syndrome was analyzed. A deletion of CAA induces the truncated protein because of stop codon.(3)The causative genes of Ataxia-telangiectasia were analyzed. (R1917X, W2491R, R2909G, IVS33+2T->A, 7883del 5)(4) The causative genes of CVID are studying.(5) NLS (nuclear localisation signal) and biological structure were analyzed. NLS was identified.

发现了几种原发性免疫缺陷的严重基因并在结构上分析。（1）鉴定出选择性IgGII D22缺乏的严重基因，并通过表达实验认识到。我们对Cγ2基因区域进行了测序，并且在两名患者中，Cγ2基因的外显子4中存在纯合的一碱基插入（1793INSG），这只是M外显子的替代剪接位点上游。突变膜结合的γ2重链失去了跨膜结构域和进化保守的细胞质结构域。考虑到几条证据表明，表明膜结合重链的完整表达对于小鼠的正常反应和分泌的免疫球蛋白的产生至关重要，我们得出结论，1793INSG在这两个兄弟姐妹中负责选择性和完整的IgGII D22偏见。这是人类选择性IgGII D22缺乏症中突变的第一条文档。（J. ClinInvest。1998。101：677-681。）（2）分析了Bloom综合征的严重基因。 CAA的缺失诱导了截短的蛋白质。（3）分析了共济失调 - 凝性的严重基因。（R1917X，W2491R，R2909G，IVS33+2T-> a，7883del 5）（4）CVID的严重基因正在研究。（5）NLS（核定位信号）和生物学结构进行了分析。确定了NLS。