Clinical, functional and genetic characterization of 16 patients suffering from chronic granulomatous disease variants - identification of 11 novel mutations in CYBB.

Chronic granulomatous disease (CGD) is a rare inherited disorder in which phagocytes lack nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. The most common form is the X-linked CGD (X91-CGD), caused by mutations in the CYBB gene. Clinical, functional and genetic characterizations of 16 CGD cases of male patients and their relatives were performed.

NOX4 is the main NADPH oxidase involved in the early stages of hematopoietic differentiation from human induced pluripotent stem cells.

Reactive oxygen species (ROS) produced in hematopoietic stem cells (HSCs) are involved in the balance between quiescence, self-renewal, proliferation and differentiation processes. However the role of NOX enzymes on the early stages of hematopoietic differentiation is poorly investigated. For that, we used induced pluripotent stem cells (iPSCs) derived from X-linked Chronic Granulomatous Disease (XCGD) patients with deficiency in NOX2, and AR22CGD patients with deficiency in p22 subunit which decreases NOX1, NOX2, NOX3 and NOX4 activities.

CYBA encoding p22(phox), the cytochrome b558 alpha polypeptide: gene structure, expression, role and physiopathology.

P22(phox) is a ubiquitous protein encoded by the CYBA gene located on the long arm of chromosome 16 at position 24, containing six exons and spanning 8.5 kb. P22(phox) is a critical component of the superoxide-generating nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs).