title: Two X-linked chronic granulomatous disease patients with unusual NADPH oxidase properties.
abstract: BACKGROUND
  Chronic granulomatous disease (CGD) is an immune deficiency syndrome caused by defects in the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, the enzyme that generates reactive oxygen species (ROS) in phagocytizing leukocytes. This study evaluates the NADPH oxidase capacity in two X-linked CGD patients with mutations in gp91(phox) that alter the regions in this membrane-bound NADPH oxidase component involved in docking of the cytosolic component p47(phox).
  
  
  METHODS
  Hydrogen peroxide and superoxide generation, bactericidal activity, and NADPH oxidase protein expression by the patients' neutrophils were measured, and genetic analysis was performed.
  
  
  RESULTS
  We report two patients, each with a novel missense mutation in CYBB, the gene that encodes gp91(phox). Surprisingly, neutrophils from these patients showed total absence of superoxide production, although they retained 13-30% of the hydrogen peroxide production capability. We speculate that this is due to direct electron transfer from flavin adenine dinucleotide (FAD) in gp91(phox) to oxygen, leading to inefficient hydrogen peroxide formation instead of efficient superoxide production.
  
  
  CONCLUSIONS
  X-linked CGD patients with mutations that alter the gp91(phox) protein in regions involved in docking of the cytosolic NADPH oxidase component p47(phox) may have higher than expected hydrogen peroxide generation capability.
authors: Pediatric Immunohematology Clinic, Meir Medical Center, 59 Tchernichovsky St., Kfar Saba, 44281, Israel. baruchw@clalit.org.il
authors: Baruch
authors: B
authors: Wolach
authors: Arnon
authors: A
authors: Broides
authors: Tal
authors: T
authors: Zeeli
authors: Ronit
authors: R
authors: Gavrieli
authors: Martin
authors: M
authors: de Boer
authors: Karin
authors: K
authors: van Leeuwen
authors: Jacov
authors: J
authors: Levy
authors: Dirk
authors: D
authors: Roos
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