An in-frame triplet deletion within the gp91-phox gene in an adult X-linked chronic granulomatous disease patient with residual NADPH-oxidase activity

Eur J Haematol. 1997 Feb;58(2):78-85. doi: 10.1111/j.1600-0609.1997.tb00928.x.


In an adult patient suffering from X-linked chronic granulomatous disease (X-CGD) with residual activity of the NADPH-oxidase we found an unusual biochemical constellation with a defective gp91-phox gene. As shown by Western blot using a specific antibody the gp91-phox protein was normal in PMN. However, NADPH-oxidase activity was reduced and no heme spectrum was detectable. By Southern blot and RFLP analysis of genomic DNA a larger defect within the gp91-phox gene was excluded. Sequencing of the gp91-phox cDNA revealed an in-frame deletion of a TTC triplet in exon VI of the gp91-phox gene. This mutation indicates the loss of one amino acid (phenylalanine 215 or 216) in the gp91-phox protein. Sequencing of genomic DNA from the heterozygous daughter of the propositus confirmed this mutation. The absence of a functional cytochrome b558-spectrum in granulocytes of the patient suggests an involvement of the phenylalanine 216 area in heme binding by gp91 phox. This is the first mutation described in a X-CGD patient with absence of a functional cytochrome b558-spectrum but with detectable gp91-phox protein and residual NADPH-oxidase activity.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Antibodies
  • Bacterial Infections
  • Cytochrome b Group / blood
  • Exons
  • Fatal Outcome
  • Female
  • Genetic Carrier Screening
  • Granulocytes / metabolism
  • Granulomatous Disease, Chronic / blood
  • Granulomatous Disease, Chronic / enzymology*
  • Granulomatous Disease, Chronic / genetics*
  • Heme / analysis
  • Humans
  • Male
  • Membrane Glycoproteins / analysis
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics*
  • Models, Structural
  • Molecular Sequence Data
  • Monocytes / drug effects
  • Monocytes / physiology
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • NADPH Oxidase 2
  • NADPH Oxidases / deficiency*
  • Neutrophils / drug effects
  • Neutrophils / physiology
  • Pedigree
  • Peptide Fragments / chemistry
  • Peptide Fragments / immunology
  • Polymorphism, Genetic*
  • Protein Conformation
  • Sequence Deletion*
  • Superoxides / blood
  • Tetradecanoylphorbol Acetate / pharmacology
  • X Chromosome
  • Zymosan / pharmacology


  • Antibodies
  • Cytochrome b Group
  • Membrane Glycoproteins
  • Peptide Fragments
  • Superoxides
  • Heme
  • N-Formylmethionine Leucyl-Phenylalanine
  • Zymosan
  • cytochrome b558
  • CYBB protein, human
  • NADPH Oxidase 2
  • NADPH Oxidases
  • Tetradecanoylphorbol Acetate