Only in the X-linked form of CGD can the (female) carriers usually, but not always, be detected by a mosaic pattern

of gp91phox-positive and -negative phagocytes, correlating with NADPH oxidase-positive and -negative cells (Table 2b). This is caused by the process of X-chromosome inactivation at an early stage of NVP-BKM120 cell line fetal development in all cells from female individuals. The X chromosome inactivated in a certain cell will also be inactive in all daughter cells derived from that cell. The inactivation process may hit either the wild-type or the mutated X chromosome, thus leaving a mixture of NADPH-competent and -incompetent haematopoietic precursor cells. However, because of the random process of X-chromosome inactivation, X-CGD carriers may show a near-normal or a near-pathological pattern in the expression or activity tests. Thus, a normal pattern does not exclude mTOR inhibitor an individual as an X-CGD carrier. Conversely, females with a near-pathological pattern often present as X-CGD patients. Carrier detection

of X-CGD is usually performed by searching for a mosaic pattern of oxidase-positive and -negative neutrophils in the NBT slide test or in the DHR flow-cytometric assay (see sections Superoxide production and Hydrogen peroxide generation). Alternatively, one can perform flow cytometry to detect gp91phox protein expression on the neutrophil surface with the anti-gp91phox monoclonal antibody 7D5 (see

section NADPH oxidase component expression). However, it must be kept in mind that up to one-third of all X-linked defects may arise from new mutations in germline cells and will therefore not always be present in the somatic cells of the mother. Thus, failure to define the mother as an X-linked carrier does not disprove the X-linked origin of the disease, or even the possibility of the mother having another child with X-CGD. If a mosaic is found in the mother but no mutation is detectable in CYBB from the patient, the X-linked G6PD gene may carry a mutation.1 Once the family-specific mutation is known, it is more reliable to perform carrier detection for any of the CGD subtypes at the DNA level (see section Mutation analysis– Gene sequencing). However, Vasopressin Receptor in case the indicator patient has a complete deletion of CYBB (on the X chromosome), the mother cannot be defined as a carrier of this deletion by simple gene sequencing. MLPA or array CGH analysis can then be applied [36, 37]. Prenatal diagnosis of CGD can be performed by analysis of the NADPH oxidase activity of fetal blood neutrophils [38], but fetal blood sampling cannot be undertaken before 16–18 weeks of gestation. Instead, analysis of DNA from amniotic fluid cells or chorionic villi provides an earlier and more reliable diagnosis for families at risk.