THE MOLECULAR ANALYSIS OF THE PRIMARY IMMUNODEFICIENCY ASSOCIATED WITH HIGH PREDISPOSITION TO CANCER

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1)Bloom syndrome and ataxia-telangiectasia are autosomal recessive human disorders characterized by immunodeficiency, genome instability and predisposition to develop cancer. Recent data reveal that the products of these two genes, BLM and ATM, interact and function together in recognizing abnormal DNA structures. To investigate the function of these two molecules in DNA damage, recognition, we generated double knockouts of ATM-/-BLM-/-in the DT4O chicken B-lymphocyte cell line. The double mutant cells were viable and exhibited a variety of characteristics of both ATM-/-and BLM-/-cells. The results suggest that ATM and BLM have largely distinct roles in recognizing different forms of damage in DNA, but also compatible with partially overlapping functions in recognizing breaks in radiation-damaged DNA.2)Hyper-IgM immunodeficiency is an immunological disorder characterized by normal or elevated serum IgM levels, and reduced serum IgG and IgA levels, due to the disruption of immunoglobulin-class switching in B cells. Activation-induced cytidine deaminase (AID) is the causative gene for the autosomal recessive form of hyper-IgM syndrome (HIGM2). We identified a point mutation leading to the stop codon in exon 5 of the AID gene (R190X) in the patient. No other mutations of the AID gene were detected in the patient. The same mutation was not detected in other members of her family. The mutation of the AID gene is assumed to be of the dominant negative form.