Hematologically important mutations : The autosomal forms of chronic granulomatous disease (third update)
(2021) In Blood Cells, Molecules, and Diseases 92.- Abstract
Chronic granulomatous disease (CGD) is an immunodeficiency disorder affecting about 1 in 250,000 individuals. CGD patients suffer from severe, recurrent bacterial and fungal infections. The disease is caused by mutations in the genes encoding the components of the leukocyte NADPH oxidase. This enzyme produces superoxide, which is subsequently metabolized to hydrogen peroxide and other reactive oxygen species (ROS). These products are essential for intracellular killing of pathogens by phagocytic leukocytes (neutrophils, eosinophils, monocytes and macrophages). The leukocyte NADPH oxidase is composed of five subunits, four of which are encoded by autosomal genes. These are CYBA, encoding p22phox, NCF1, encoding... (More)
Chronic granulomatous disease (CGD) is an immunodeficiency disorder affecting about 1 in 250,000 individuals. CGD patients suffer from severe, recurrent bacterial and fungal infections. The disease is caused by mutations in the genes encoding the components of the leukocyte NADPH oxidase. This enzyme produces superoxide, which is subsequently metabolized to hydrogen peroxide and other reactive oxygen species (ROS). These products are essential for intracellular killing of pathogens by phagocytic leukocytes (neutrophils, eosinophils, monocytes and macrophages). The leukocyte NADPH oxidase is composed of five subunits, four of which are encoded by autosomal genes. These are CYBA, encoding p22phox, NCF1, encoding p47phox, NCF2, encoding p67phox and NCF4, encoding p40phox. This article lists all mutations identified in these genes in CGD patients. In addition, cytochrome b558 chaperone-1 (CYBC1), recently recognized as an essential chaperone protein for the expression of the X-linked NADPH oxidase component gp91phox (also called Nox2), is encoded by the autosomal gene CYBC1. Mutations in this gene also lead to CGD. Finally, RAC2, a small GTPase of the Rho family, is needed for activation of the NADPH oxidase, and mutations in the RAC2 gene therefore also induce CGD-like symptoms. Mutations in these last two genes are also listed in this article.
(Less)
- author
- organization
- publishing date
- 2021-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Autosomal recessive, Chronic granulomatous disease, Mutation, NADPH oxidase, Polymorphism
- in
- Blood Cells, Molecules, and Diseases
- volume
- 92
- article number
- 102596
- publisher
- Elsevier
- external identifiers
-
- scopus:85115191688
- pmid:34547651
- ISSN
- 1079-9796
- DOI
- 10.1016/j.bcmd.2021.102596
- language
- English
- LU publication?
- yes
- id
- 3b629163-d689-44cf-96b4-1c8c0eb26eb8
- date added to LUP
- 2021-12-22 10:46:09
- date last changed
- 2024-04-20 18:06:08
@article{3b629163-d689-44cf-96b4-1c8c0eb26eb8, abstract = {{<p>Chronic granulomatous disease (CGD) is an immunodeficiency disorder affecting about 1 in 250,000 individuals. CGD patients suffer from severe, recurrent bacterial and fungal infections. The disease is caused by mutations in the genes encoding the components of the leukocyte NADPH oxidase. This enzyme produces superoxide, which is subsequently metabolized to hydrogen peroxide and other reactive oxygen species (ROS). These products are essential for intracellular killing of pathogens by phagocytic leukocytes (neutrophils, eosinophils, monocytes and macrophages). The leukocyte NADPH oxidase is composed of five subunits, four of which are encoded by autosomal genes. These are CYBA, encoding p22<sup>phox</sup>, NCF1, encoding p47<sup>phox</sup>, NCF2, encoding p67<sup>phox</sup> and NCF4, encoding p40<sup>phox</sup>. This article lists all mutations identified in these genes in CGD patients. In addition, cytochrome b<sub>558</sub> chaperone-1 (CYBC1), recently recognized as an essential chaperone protein for the expression of the X-linked NADPH oxidase component gp91<sup>phox</sup> (also called Nox2), is encoded by the autosomal gene CYBC1. Mutations in this gene also lead to CGD. Finally, RAC2, a small GTPase of the Rho family, is needed for activation of the NADPH oxidase, and mutations in the RAC2 gene therefore also induce CGD-like symptoms. Mutations in these last two genes are also listed in this article.</p>}}, author = {{Roos, Dirk and van Leeuwen, Karin and Hsu, Amy P. and Priel, Debra Long and Begtrup, Amber and Brandon, Rhonda and Rawat, Amit and Vignesh, Pandiarajan and Madkaikar, Manesha and Stasia, Marie José and Bakri, Faris Ghalib and de Boer, Martin and Roesler, Joachim and Köker, Nezihe and Köker, M. Yavuz and Jakobsen, Marianne and Bustamante, Jacinta and Garcia-Morato, Maria Bravo and Shephard, Juan Luis Valdivieso and Cagdas, Deniz and Tezcan, Ilhan and Sherkat, Roya and Mortaz, Esmaeil and Fayezi, Abbas and Shahrooei, Mohammad and Wolach, Baruch and Blancas-Galicia, Lizbeth and Kanegane, Hirokazu and Kawai, Toshinao and Condino-Neto, Antonio and Vihinen, Mauno and Zerbe, Christa S. and Holland, Steven M. and Malech, Harry L. and Gallin, John I. and Kuhns, Douglas B.}}, issn = {{1079-9796}}, keywords = {{Autosomal recessive; Chronic granulomatous disease; Mutation; NADPH oxidase; Polymorphism}}, language = {{eng}}, publisher = {{Elsevier}}, series = {{Blood Cells, Molecules, and Diseases}}, title = {{Hematologically important mutations : The autosomal forms of chronic granulomatous disease (third update)}}, url = {{http://dx.doi.org/10.1016/j.bcmd.2021.102596}}, doi = {{10.1016/j.bcmd.2021.102596}}, volume = {{92}}, year = {{2021}}, }