The causative genes and biological structure analyses of primary immunodeficiencies.

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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.