title: The search for a genetic defect in Polish patients with chronic granulomatous disease.
abstract: BACKGROUND
  Chronic granulomatous disease (CGD)is a rare inherited disorder in which phagocytic cells are unable to generate superoxide anions. Patients with CGD are predisposed to recurrent bacterial and fungal infections because the superoxide-generating NADPH oxidase activity is needed for efficient killing of microbes. Among the at least 5 subunits cre-ating a functional NADPH oxidase, a molecular defect located in any of the gp91phox, p22phox, p47phox, or p67phox subunits may cause CGD.
  
  
  METHODS
  In this study,8 patients were diagnosed with CGD on the basis of clinical findings and absence of nitroblue tetrazolium reduction in phagocytes. Southern blot analysis, GeneScan, and direct sequencing were performed to define particular DNA mutations.
  
  
  RESULTS
  Among 6 X-linked CGD (X-CGD)patients, 4 different mutations were identified in the X-linked CYBB gene (encoding gp91phox)by direct sequencing. A novel missense mutation, located in the NADPH-binding region of gp91phox,was found in 2 brothers. One frameshift 1578delA, one splicing 252G->A mutation, and one partial gene deletion were also identified. The molecular defect in the NCF1 gene (encoding p47phox)was established in 2 patients. One was DeltaGT/DeltaGT homozygote, the other carried, besides this GT deletion on one allele, a unique Phe118stop mutation on the other.
  
  
  CONCLUSIONS
  In general, the X-CGD patients within the group followed a more severe clinical course than the patients with an NCF1 defect. However, the lack of a straightforward genotype phenotype correlation indicates that the clinical severity of CGD depends also on other antimicrobial host-defense systems.
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland. mjurkowska@imid.med.pl
authors.forename: Monika
authors.initials: M
authors.lastname: Jurkowska
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kurenko-Deptuch
authors.forename: Jerzy
authors.initials: J
authors.lastname: Bal
authors.forename: Dirk
authors.initials: D
authors.lastname: Roos
mesh_terms: D002675:Child, Preschool; D041321:Chromosomes, Human, X; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006105:Granulomatous Disease, Chronic / Q000235:genetics*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D009154:Mutation; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics*; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics*; D011044:Poland
chemical_list: D008562:Membrane Glycoproteins; D010750:Phosphoproteins; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1