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 gp91(phox), 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 gp91(phox), 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 degrees-CGD in this family. These molecular findings help to explain the early onset and severe phenotype in this X-CGD kindred.
Barese
Cecilia N
CN
Division of Immunology, Hospital de Niños Dr. Ricardo Gutiérrez, Associated Hospital to the Universidad de Buenos Aires, Buenos Aires, Argentina. cbarese@iupui.edu
Copelli
Silvia B
SB
De Matteo
Elena
E
Zandomeni
Rubén
R
Salgueiro
Fabián
F
Di Giovanni
Daniela
D
Heyworth
Paul
P
Rivas
Eva María
EM
D002648:Child; D002761:Cholangitis / Q000209:etiology / Q000473:pathology; D006105:Granulomatous Disease, Chronic / Q000235:genetics*; D006801:Humans; D008100:Liver Abscess / Q000209:etiology / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D009154:Mutation; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics*; D009504:Neutrophils / Q000378:metabolism; D022821:RNA Splice Sites
D008562:Membrane Glycoproteins; D022821:RNA Splice Sites; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases