Chronic granulomatous disease, the McLeod phenotype and the contiguous gene deletion syndrome-a review

Primary immune deficiencies can involve defects in phagocyte function, resulting in Chronic granulomatous disease (CGD) [1,2]. CGD is characterized by repeated infections with bacterial and fungal pathogens, as well as the formation of granulomas [1-4]. In this disease, the NADPH oxidase system is dysfunctional due to specific gene mutations, culminating in an inability of the phagocyte to eliminate pathogenic organisms. Typically, this defect in phagocyte function leads to serious infections including Staphylococcus aureus, Pseudomonas species, Nocardia species, fungi such as Aspergillus species, and Candida albicans. Significant morbidity and mortality may result.The genetic defect in CGD can be transmitted in either an X-linked or autosomal recessive manner [1,5-7]. Genes regulating NADPH assembly and function are most commonly affected. When X-linked disease occurs, deletion of the contiguous genes that border the gene on the X chromosome that regulates NADPH function can result in the "contiguous X-chromosome gene deletion syndrome" [8-12]. Mutations extending into these surrounding genes may result in Duchenne muscular dystrophy (DMD) or Retinitis pigmentosa [13,14]. Other conditions, such as the McLeod syndrome, may also result in such patients [15-18]. In some selected situations, mutations in other innate immune system genes such as the complement pathway genes (especially mannose binding lectin) may further complicate disease severity and management [19].X-linked CGD is responsible for the majority (> 60%) of the CGD cases seen in the United States [2,20]. The X-linked type is caused by a mutation in the gp91phox gene, which is also referred to as the cytochrome b-245 beta polypeptide (CYBB) gene. Autosomal recessive CGD is seen in the remaining 35% of cases and arises due to mutations of the other components of the NADPH oxidase system [1,2,5-7]. These mutations include p22phox , p67phox, and p47phox . Of these, the dominant mutation observed is in the p2