THE MOLECULAR GENETICS OF CHRONIC GRANULOMATOUS DISEASE

CONDINO-NETO A. MD, PhD.(1)

(1)Department of Immunology. Institute of Biomedical Sciences, University of São Paulo, Brazil.

Phagocytes, such as macrophages and granulocytes, contain a membrane-associated NADPH oxidase that produces superoxide and other reactive oxygen intermediates responsible for microbicidal, tumoricidal, and inflammatory activities. Defects in oxidase activity in chronic granulomatous disease (CGD) lead to severe, life-threatening infections that demonstrate the prime importance of the oxygen-dependent microbicidal system in host defense. The estimate incidence of this disease is 1/250.000 live births per year. The molecular defects causing CGD are generally due to the absence, low expression or malfunctioning of one of the NADPH oxidase components. The X-linked form of the disease is caused by defects in the heavy chain of the cytochrome b588 component (gp91-phox) and accounts 56% of the cases. The autosomal recessive forms are caused by defects in one of the cytosolic components of the NADPH oxidase (p47-phox or p67-phox, respectively 33% and 5% of the cases); or even the cytochrome b588 light chain component (p22-phox , 6% of the cases) to date, no CGD patients have been reported with defects in p40-phox, rap1A, rac1, or GDI components. The diversity of these mutations and the multiple affected genes give an explanation for the clinical and genetic heterogeneity of CGD. Our aim is to show the current investigation about the molecular genetics of CGD patients in Brazil and Latin America in addition to new findings about the regulation of the NADPH oxidase by transcription factors and their connection with other immunodeficiencies.

CORRESPONDENCE TO:

Antonio Condino MD PhD, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo. Lineu Prestes Avenue 1730; São Paulo - SP. CEP 05508-900. Brazil. Email: condino@icb.usp.br