Genetics of primary immunodeficiency diseases.
The primary immunodeficiencies are a heterogeneous group of disorders that affect either the development or the function of the immune system. In the last ten years, the genes responsible for many of the most common and best studied immunodeficiencies have been identified. As might be expected, the expression of most of these genes is limited to the hematopoietic system. Although most are members of gene families, their association with disease indicates that they do not perform redundant functions. Some immunodeficiencies involve the effector functions of the immune system, for example the NADPH oxidase system or perforin; however, a striking number of the disorders involve signal transduction pathways. These include defects in ligands, transmembrane receptors, kinases, adaptor proteins and transcription factors. Mutations for each disorder tend to be highly variable and the specific mutation in a gene is only one of the factors that influence the clinical phenotype. Polymorphic variations in susceptibility genes may also contribute to the disease phenotype. Not all genes responsible for immunodeficiency have been identified. As many as 20 to 30% of patients with clinical and laboratory evidence of single gene defects of the immune system do not fit any well described clinical disorder.
Department of Pediatrics, University of Tennessee College of Medicine, Memphis, TN, USA. maryellen.conley@stjude.org
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D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D019255:NADPH Oxidases / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
D019255:NADPH Oxidases