Abstract
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
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Case Reports
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Amino Acid Sequence
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Antibodies
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Bacterial Infections
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Cytochrome b Group / blood
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Exons
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Fatal Outcome
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Female
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Genetic Carrier Screening
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Granulocytes / metabolism
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Granulomatous Disease, Chronic / blood
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Granulomatous Disease, Chronic / enzymology*
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Granulomatous Disease, Chronic / genetics*
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Heme / analysis
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Humans
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Male
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Membrane Glycoproteins / analysis
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / genetics*
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Models, Structural
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Molecular Sequence Data
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Monocytes / drug effects
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Monocytes / physiology
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N-Formylmethionine Leucyl-Phenylalanine / pharmacology
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NADPH Oxidase 2
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NADPH Oxidases / deficiency*
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Neutrophils / drug effects
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Neutrophils / physiology
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Pedigree
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Peptide Fragments / chemistry
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Peptide Fragments / immunology
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Polymorphism, Genetic*
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Protein Conformation
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Sequence Deletion*
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Superoxides / blood
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Tetradecanoylphorbol Acetate / pharmacology
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X Chromosome
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Zymosan / pharmacology
Substances
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Antibodies
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Cytochrome b Group
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Membrane Glycoproteins
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Peptide Fragments
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Superoxides
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Heme
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N-Formylmethionine Leucyl-Phenylalanine
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Zymosan
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cytochrome b558
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CYBB protein, human
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NADPH Oxidase 2
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NADPH Oxidases
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Tetradecanoylphorbol Acetate