We have restudied two kindreds that formed the basis of the original report of autosomal recessive chronic granulomatous disease (CGD) associated with leukocyte glutathione peroxidase deficiency. Case 1 from the original study and the surviving brother of the originally reported case 2 both have severe CGD, with no detectable respiratory burst activity in purified intact neutrophils. However, their leukocytes exhibit normal glutathione peroxidase enzyme activity and gene expression. Examination of phagocyte nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase components known to be defective in CGD reveals no detectable cytochrome b558 nor any membrane activity in a cell-free NADPH oxidase assay system. Molecular analysis of the genes encoding cytochrome b558 subunits shows, in case 1, a C-->T substitution at nucleotide 688 of the gene encoding the gp91-phox subunit of cytochrome b558, resulting in a termination signal in place of Arginine-226. Levels of gp91-phox mRNA are markedly decreased despite normal levels of gene transcription, indicating a post- transcriptional effect of the nonsense mutation on mRNA processing or stability. The X-linked form of CGD developed in this cytogenetically normal female due to the uniform inactivation of the normal X chromosome in her granulocytes, indicated by the expression in her granulocyte mRNA of only one allele of a glucose-6-phosphate dehydrogenase polymorphisms for which she is heterozygous in genomic DNA. Case 2 (of the present study) has distinct mutations in each allele of the p22-phox gene.(ABSTRACT TRUNCATED AT 250 WORDS)
Skip Nav Destination
ARTICLES|
December 1, 1994
Chronic granulomatous disease and glutathione peroxidase deficiency, revisited
PE Newburger,
PE Newburger
Department of Pediatrics, University of Massachusetts Medical School, Worcester 01655.
Search for other works by this author on:
SE Malawista,
SE Malawista
Department of Pediatrics, University of Massachusetts Medical School, Worcester 01655.
Search for other works by this author on:
MC Dinauer,
MC Dinauer
Department of Pediatrics, University of Massachusetts Medical School, Worcester 01655.
Search for other works by this author on:
T Gelbart,
T Gelbart
Department of Pediatrics, University of Massachusetts Medical School, Worcester 01655.
Search for other works by this author on:
RC Woodman,
RC Woodman
Department of Pediatrics, University of Massachusetts Medical School, Worcester 01655.
Search for other works by this author on:
S Chada,
S Chada
Department of Pediatrics, University of Massachusetts Medical School, Worcester 01655.
Search for other works by this author on:
Q Shen,
Q Shen
Department of Pediatrics, University of Massachusetts Medical School, Worcester 01655.
Search for other works by this author on:
G van Blaricom,
G van Blaricom
Department of Pediatrics, University of Massachusetts Medical School, Worcester 01655.
Search for other works by this author on:
PG Quie,
PG Quie
Department of Pediatrics, University of Massachusetts Medical School, Worcester 01655.
Search for other works by this author on:
JT Curnutte
JT Curnutte
Department of Pediatrics, University of Massachusetts Medical School, Worcester 01655.
Search for other works by this author on:
Blood (1994) 84 (11): 3861–3869.
Citation
PE Newburger, SE Malawista, MC Dinauer, T Gelbart, RC Woodman, S Chada, Q Shen, G van Blaricom, PG Quie, JT Curnutte; Chronic granulomatous disease and glutathione peroxidase deficiency, revisited. Blood 1994; 84 (11): 3861–3869. doi: https://doi.org/10.1182/blood.V84.11.3861.bloodjournal84113861
Download citation file:
December 1 1994
Advertisement intended for health care professionals
Cited By
Advertisement intended for health care professionals
This feature is available to Subscribers Only
Sign In or Create an Account Close Modal