Genetic variants of chronic granulomatous disease: Prevalence of deficiencies of two cytosolic components of the NADPH oxidase system

Robert A Clark, H. L. Malech, J. I. Gallin, H. Nunoi, B. D. Volpp, D. W. Pearson, W. M. Nauseef, J. T. Curnutte

Research output: Contribution to journalArticle

154 Citations (Scopus)

Abstract

Chronic granulomatous disease, a syndrome of recurrent infections and failure of oxidative microbicidal activity in phagocytes, results from defects in the gene for one of several components of an oxidase system that can undergo activation. To determine the relative prevalence of certain of the genetic variants of this disorder, we used immunoblotting to detect two specific neutrophil cytosol proteins of 47 and 67 kd recently shown to be required for oxidase activation. Chronic granulomatous disease is usually an X-linked disorder associated with the absence of membrane cytochrome b558. Of our 94 patients with chronic granulomatous disease, however, 36 had a phenotype characterized by autosomal inheritance, normal membrane oxidase components (including cytochrome b558), and functionally defective cytosolic activity in a cell-free oxidase system. We studied 25 of these 36 patients and found that 22 lacked the 47-kd cytosolic protein, and the remaining 3 were missing the 67-kd component. Patients with chronic granulomatous disease whose functional defect was localized to the neutrophil membrane (classic X-linked cytochrome b-negative type and two other rare variants) had normal amounts of both cytosolic components. We estimate that approximately 33 percent of all patients with chronic granulomatous disease are missing the 47-kd cytosolic oxidase component and about 5 percent of patients are missing the 67-kd component. Chronic granulomatous disease caused by a defect in any cytosolic factors other than the 47-kd and 67-kd proteins, if it exists, is apparently rare.

Original languageEnglish (US)
Pages (from-to)647-652
Number of pages6
JournalNew England Journal of Medicine
Volume321
Issue number10
StatePublished - 1989
Externally publishedYes

Fingerprint

Chronic Granulomatous Disease
NADPH Oxidase
Oxidoreductases
Membranes
Neutrophils
Cytochrome b Group
Inborn Genetic Diseases
Proteins
Cell-Free System
Phagocytes
Immunoblotting
Cytosol
Phenotype
Infection
Genes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Clark, R. A., Malech, H. L., Gallin, J. I., Nunoi, H., Volpp, B. D., Pearson, D. W., ... Curnutte, J. T. (1989). Genetic variants of chronic granulomatous disease: Prevalence of deficiencies of two cytosolic components of the NADPH oxidase system. New England Journal of Medicine, 321(10), 647-652.

Genetic variants of chronic granulomatous disease : Prevalence of deficiencies of two cytosolic components of the NADPH oxidase system. / Clark, Robert A; Malech, H. L.; Gallin, J. I.; Nunoi, H.; Volpp, B. D.; Pearson, D. W.; Nauseef, W. M.; Curnutte, J. T.

In: New England Journal of Medicine, Vol. 321, No. 10, 1989, p. 647-652.

Research output: Contribution to journalArticle

Clark, RA, Malech, HL, Gallin, JI, Nunoi, H, Volpp, BD, Pearson, DW, Nauseef, WM & Curnutte, JT 1989, 'Genetic variants of chronic granulomatous disease: Prevalence of deficiencies of two cytosolic components of the NADPH oxidase system', New England Journal of Medicine, vol. 321, no. 10, pp. 647-652.
Clark, Robert A ; Malech, H. L. ; Gallin, J. I. ; Nunoi, H. ; Volpp, B. D. ; Pearson, D. W. ; Nauseef, W. M. ; Curnutte, J. T. / Genetic variants of chronic granulomatous disease : Prevalence of deficiencies of two cytosolic components of the NADPH oxidase system. In: New England Journal of Medicine. 1989 ; Vol. 321, No. 10. pp. 647-652.
@article{27d1377f17fb47acbc3e145d4d4d702e,
title = "Genetic variants of chronic granulomatous disease: Prevalence of deficiencies of two cytosolic components of the NADPH oxidase system",
abstract = "Chronic granulomatous disease, a syndrome of recurrent infections and failure of oxidative microbicidal activity in phagocytes, results from defects in the gene for one of several components of an oxidase system that can undergo activation. To determine the relative prevalence of certain of the genetic variants of this disorder, we used immunoblotting to detect two specific neutrophil cytosol proteins of 47 and 67 kd recently shown to be required for oxidase activation. Chronic granulomatous disease is usually an X-linked disorder associated with the absence of membrane cytochrome b558. Of our 94 patients with chronic granulomatous disease, however, 36 had a phenotype characterized by autosomal inheritance, normal membrane oxidase components (including cytochrome b558), and functionally defective cytosolic activity in a cell-free oxidase system. We studied 25 of these 36 patients and found that 22 lacked the 47-kd cytosolic protein, and the remaining 3 were missing the 67-kd component. Patients with chronic granulomatous disease whose functional defect was localized to the neutrophil membrane (classic X-linked cytochrome b-negative type and two other rare variants) had normal amounts of both cytosolic components. We estimate that approximately 33 percent of all patients with chronic granulomatous disease are missing the 47-kd cytosolic oxidase component and about 5 percent of patients are missing the 67-kd component. Chronic granulomatous disease caused by a defect in any cytosolic factors other than the 47-kd and 67-kd proteins, if it exists, is apparently rare.",
author = "Clark, {Robert A} and Malech, {H. L.} and Gallin, {J. I.} and H. Nunoi and Volpp, {B. D.} and Pearson, {D. W.} and Nauseef, {W. M.} and Curnutte, {J. T.}",
year = "1989",
language = "English (US)",
volume = "321",
pages = "647--652",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "10",

}

TY - JOUR

T1 - Genetic variants of chronic granulomatous disease

T2 - Prevalence of deficiencies of two cytosolic components of the NADPH oxidase system

AU - Clark, Robert A

AU - Malech, H. L.

AU - Gallin, J. I.

AU - Nunoi, H.

AU - Volpp, B. D.

AU - Pearson, D. W.

AU - Nauseef, W. M.

AU - Curnutte, J. T.

PY - 1989

Y1 - 1989

N2 - Chronic granulomatous disease, a syndrome of recurrent infections and failure of oxidative microbicidal activity in phagocytes, results from defects in the gene for one of several components of an oxidase system that can undergo activation. To determine the relative prevalence of certain of the genetic variants of this disorder, we used immunoblotting to detect two specific neutrophil cytosol proteins of 47 and 67 kd recently shown to be required for oxidase activation. Chronic granulomatous disease is usually an X-linked disorder associated with the absence of membrane cytochrome b558. Of our 94 patients with chronic granulomatous disease, however, 36 had a phenotype characterized by autosomal inheritance, normal membrane oxidase components (including cytochrome b558), and functionally defective cytosolic activity in a cell-free oxidase system. We studied 25 of these 36 patients and found that 22 lacked the 47-kd cytosolic protein, and the remaining 3 were missing the 67-kd component. Patients with chronic granulomatous disease whose functional defect was localized to the neutrophil membrane (classic X-linked cytochrome b-negative type and two other rare variants) had normal amounts of both cytosolic components. We estimate that approximately 33 percent of all patients with chronic granulomatous disease are missing the 47-kd cytosolic oxidase component and about 5 percent of patients are missing the 67-kd component. Chronic granulomatous disease caused by a defect in any cytosolic factors other than the 47-kd and 67-kd proteins, if it exists, is apparently rare.

AB - Chronic granulomatous disease, a syndrome of recurrent infections and failure of oxidative microbicidal activity in phagocytes, results from defects in the gene for one of several components of an oxidase system that can undergo activation. To determine the relative prevalence of certain of the genetic variants of this disorder, we used immunoblotting to detect two specific neutrophil cytosol proteins of 47 and 67 kd recently shown to be required for oxidase activation. Chronic granulomatous disease is usually an X-linked disorder associated with the absence of membrane cytochrome b558. Of our 94 patients with chronic granulomatous disease, however, 36 had a phenotype characterized by autosomal inheritance, normal membrane oxidase components (including cytochrome b558), and functionally defective cytosolic activity in a cell-free oxidase system. We studied 25 of these 36 patients and found that 22 lacked the 47-kd cytosolic protein, and the remaining 3 were missing the 67-kd component. Patients with chronic granulomatous disease whose functional defect was localized to the neutrophil membrane (classic X-linked cytochrome b-negative type and two other rare variants) had normal amounts of both cytosolic components. We estimate that approximately 33 percent of all patients with chronic granulomatous disease are missing the 47-kd cytosolic oxidase component and about 5 percent of patients are missing the 67-kd component. Chronic granulomatous disease caused by a defect in any cytosolic factors other than the 47-kd and 67-kd proteins, if it exists, is apparently rare.

UR - http://www.scopus.com/inward/record.url?scp=0024453201&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024453201&partnerID=8YFLogxK

M3 - Article

C2 - 2770793

AN - SCOPUS:0024453201

VL - 321

SP - 647

EP - 652

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 10

ER -