Hematologically important mutations: X-linked chronic granulomatous disease (third update)

Abstract

Chronic Granulomatous Disease (CGD) is an immunodeficiency disorder affecting about 1 in 250,000 individuals. The disease is caused by a lack of superoxide production by the leukocyte enzyme NADPH oxidase. Superoxide is used to kill phagocytosed micro-organisms in neutrophils, eosinophils, monocytes and macrophages. The leukocyte NADPH oxidase is composed of five subunits, of which the enzymatic component is gp91-phox, also called Nox2. This protein is encoded by the CYBB gene on the × chromosome. Mutations in this gene are found in about 70% of all CGD patients. This article lists all mutations identified in CYBB in the X-linked form of CGD. Moreover, apparently benign polymorphisms in CYBB are also given, which should facilitate the recognition of future disease-causing mutations.

Monocyte/macrophage-Specific NADPH Oxidase Contributes to Antimicrobial Host Defense in X-CGD

“…The underlying CYBB mutation of c.1016C>A (p.P339H) in the present patient was previously reported in 10 families of X-CGD patients [28][29][30][31][32][33] (http://structure.bmc.lu.se/idbase/) ( Table 2). The patients from nine families were all classified into classical X-CGD.…”

Rapid Detection of Intracellular p47phox and p67phox by Flow Cytometry; Useful Screening Tests for Chronic Granulomatous Disease

“…Mutations in the gp91phox gene cause X-linked CGD and account for approximately 70% of all cases [4]. The remaining 30% are due to mutations in the other subunit and are inherited in an autosomal recessive manner [1].…”

“…The NADPH oxidase is a multicomponent system including a membrane-bound flavocytochrome b558, comprised of gp91phox and p22phox, cytosolic components, comprised of p40phox, p47phox, and p67phox, and a small GTP-binding protein comprised of Rac1 or Rac2 [1,2]. About 70% of CGD cases are caused by mutations in the CYBB gene that encodes gp91phox and is located at Xp21.1 [4]. The remaining 30% of cases include four other subgroups of the disease, all of which are inherited in an autosomal recessive manner [1,2].…”

Reconstitución inmune exitosa mediante trasplante de células madre hematopoyéticas en un paciente colombiano afectado con enfermedad granulomatosa crónica

“…Aproximadamente, el 10 % de los pacientes con la enfermedad presentan grandes deleciones que afectan uno o más exones del gen, e incluso estas pueden abarcar genes contiguos como el XK (síndrome de McLeod), el OTC (transcarbamilasa de ornitina), el DMD (distrofia muscular de Duchenne) y el RP (retinitis pigmentosa), entre otros (23,24). En el presente estudio no se pudieron establecer los puntos de quiebre 5' y 3' de la deleción, por lo tanto, no fue posible establecer el rango de genes afectados, incluidos los ya mencionados.…”