Molecular characterization of a novel splice site mutation within the CYBB gene leading to X-linked chronic granulomatous disease

Chronic granulomatous disease (CGD) is a primary immunodeficiency that affects the oxidative mechanism of microbial killing of phagocytic cells. The defect is characterized by a lack or severely reduced superoxide anion (O2−) production by phagocytes. Seventy percent of CGD cases are X‐linked (X‐CGD) and they are caused by mutations in the gene encoding for gp91phox, one of the two subunits of the flavocytochrome b558 of the NADPH oxidase. We identified an abnormal transcript arising from a novel splice site mutation within the gene encoding gp91phox, which suggested that the mutation affected normal mRNA splicing. Thus, the effect of this mutation leads to the complete absence of the flavocytochrome b558 in neutrophil membranes, which caused the biochemical phenotype X91°‐CGD in this family. These molecular findings help to explain the early onset and severe phenotype in this X‐CGD kindred. © 2004 Wiley‐Liss, Inc.