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Molecular characterization of a novel splice site mutation within the CYBB gene leading to X‐linked chronic granulomatous disease
Author(s) -
Barese Cecilia N.,
Copelli Silvia B.,
Matteo Elena De,
Zandomeni Rubén,
Salgueiro Fabián,
Giovanni Daniela Di,
Heyworth Paul,
Rivas Eva María
Publication year - 2005
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.20204
Subject(s) - chronic granulomatous disease , mutation , primary immunodeficiency , gene , rna splicing , phenotype , genetics , superoxide , nadph oxidase , microbiology and biotechnology , biology , immunology , medicine , rna , enzyme , reactive oxygen species , biochemistry , immune system
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 (O 2 − ) 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°‐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.