Studies for causative genes on primary immunodeficiency

在原发免疫缺陷中有许多疾病。这项研究的目的是调查致病基因和基因突变。结果表明，常见变异型免疫缺陷患者B细胞免疫球蛋白重链同型开关的缺陷是由于生殖系CGamma转录物合成失败所致，这是由于特定区域染色质结构开放缺陷所致。提示IgG2缺陷，干扰素信使RNA表达降低在该患者的IgG2缺陷中起重要作用。克隆了BLM基因(Bloom综合征基因)。BLm基因全长4437bp，编码1417个氨基酸残基。同胞病例均为CAA缺失(HOMO)。结果，TAA序列显示为终止密码子。共济失调-毛细血管扩张症是一种常染色体隐性遗传病。分离到ATM基因(共济失调-毛细血管扩张基因)。ATM基因全长9867bp，编码3056个氨基酸残基。这些病例表现为突变或TattA缺失。这些突变等发生信号转导和细胞周期异常等功能异常。

There are many diseases in primary immunodeficiencies. The purpose of this study is to investigate the causative genes and the mutations in the genes. The results obtained are as follows.The defects of the immunoglobulin heavy chain isotype switch in the common variable immunodeficiency patient's (decreased IgG and IgA) B cells were due to failure in the synthesis of germ-line Cgamma transcripts, and this were caused by defects in opening of the chromatin structures of specific regions.Concerning IgG2 deficiency, the reduced expression of imterferongamma messenger RNA playd important role in the IgG2 deficiency of these patients.Bloom syndrome is an antosomal recessive genetic disorder. BLM gene (Bloom syndrome gene) was isolated. BLM cDNA is 4437 bp long and represents a 1417 amino acid residue peptide. The sib cases showed the CAA deletion (homo). As a result, the TAA sequence playd as the stop codon.Ataxia-telangiectasia is an autosomal recesive genetic disorder. ATM gene (ataxia-telangiectasia gene) was isolated. ATM cDNA is 9867 bp long and represents a 3056 amino acid residue peptide. The cases exhibited the mutation or TATTA deletion. These mutations etc occurred the functional abnormalities such as signaling and cell cycle abnormalities.