Mutations in CYBA or CYBB, encoding p22phox or NOX2, respectively, lead to because of the absence of cytb in both cases. This means that the synthesis of both subunits is essential for the maturation of cytb. CGD is a rare inherited disorder in which phagocytic cells are unable to kill pathogens during an infection. Patients suffer from severe and recurrent infections early in childhood. Actually, the main treatment is antibiotic and antifungal prophylaxis. Allogenic bone marrow transplantation is possible and genetic therapy is currently under development. The most frequent CGD form is X-linked CGD caused by mutations in CYBB (60% of cases). Mutations in the CYBA gene encoding p22phox are extremely rare (about 6%) and lead to AR-CGD220. However, in countries such as Turkey, Tunisia, Morocco and Jordan AR inheritance can be the predominant form because of the high rate of consanguinity. As of 2010, 55 different mutations of CYBA have been identified. Most CYBA mutations result in the absence of p22phox expression (AR-CGD220). The only missense mutation leading to a normal expression of a nonfunctional p22phox protein is Pro156Gln (AR-CGD22+) located in the potential cytosolic C-terminal tail of p22phox. This mutation in the PRR of p22phox disrupted the interaction between p22phox and p47phox, confirming the importance of this domain in the oxidase activation in neutrophils. Since p22phox is ubiquitous and associated with different NOXs, it could be logical that CGD patients suffer from the consequences of the absence of p22phox expression in tissues. However it is far from being evident. One possibility could be that the humans may be able to compensate for the absence of p22phox and/or NOXs in cells and tissues other than phagocytes. Given the rarity of the AR-CGD220 forms, information on the severity of this type of CGD is difficult to establish. A relationship between the presence of residual ROS production and the survival of CGD patients has been found. In case of CYBA mutations leading to the absence of p22phox, NOX2 expression is also absent and disables cytochrome b558, the redox element of the NADPH oxidase complex. Therefore, these mutations behave similarly to severe X-CGD. The molecular and phenotypic characterization of a p22phox-deficient mouse strain with the Tyr121His missense mutation in CYBA has been described. The p22phox deficiency results in the clinical and biological characteristics of CGD as well as a severe balance disorder in these mice. As the site of p22phox expression is in the inner ear, p22phox has been proposed as being involved in the control of vestibular organogenesis. In addition, mutations of NOX3 in head-tilt mice were associated with vestibular defects. Yet the in vivo relevance of p22phox for NOX3 function remains uncertain because AR-CGD220 patients do not suffer from vestibular dysfunction (personal data). One possibility could be that the human brain may be able to compensate the balance defect. In Matsumoto Eosinophilia Shinshu (MES) rats a loss-of-function mutation in CYBA was responsible for spontaneous and severe blood eosinophilia. These rats suffered from a balance defect due to a leak of otoconia in the inner ear, like nmf333 mice. In addition, MES rats retained normal innate immune defense against Staphylococcus aureus infection probably because of the hypereosinophilia. However, the mechanisms by which CYBA mutations lead to eosinophilia remain unknown.. Cytochrome b-245 light chain is a protein that in humans is encoded by the CYBA gene involved in superoxide production and phagocytosis. Cytochrome b-245 is composed of a light chain (alpha) and a heavy chain (beta).. Cytochrome b (-245) is composed of cytochrome b alpha (CYBA) and beta (CYBB) chain. It has been proposed as a primary component of the microbicidal oxidase system of phagocytes. CYBB deficiency is one of five described biochemical defects associated with chronic granulomatous disease (CGD). In this.