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Hematologically important mutations: X-linked chronic granulomatous disease (fourth update)

2021; Elsevier BV; Volume: 90; Linguagem: Inglês

10.1016/j.bcmd.2021.102587

1096-0961

Dirk Roos, Karin van Leeuwen, Amy P. Hsu, Debra Long Priel, Amber Begtrup, Rhonda Brandon, Marie José Stasia, Faris G. Bakri, Nezihe Köker, Mustafa Yavuz Köker, Manisha Madkaika, Martin de Boer, María Bravo García‐Morato, Juan Luis Valdivieso Shephard, Joachim Roesler, Hirokazu Kanegane, Toshinao Kawai, Gigliola Di Matteo, Mohammad Shahrooei, Jacinta Bustamante, Amit Rawat, Pandiarajan Vignesh, Esmaeil Mortaz, Abbas Fayezi, Deniz Çağdaş, İlhan Tezcan, Maleewan Kitcharoensakkul, Mary C. Dinauer, Isabelle Meyts, Baruch Wolach, Antônio Condino‐Neto, Christa S. Zerbe, Steven M. Holland, Harry L. Malech, John I. Gallin, Douglas B. Kuhns,

Calcium signaling and nucleotide metabolism

Chronic granulomatous disease (CGD) is an immunodeficiency disorder affecting about 1 in 250,000 individuals. CGD patients suffer from severe bacterial and fungal infections. The disease is caused by a lack of superoxide production by the leukocyte enzyme NADPH oxidase. Superoxide and subsequently formed other reactive oxygen species (ROS) are instrumental in killing phagocytosed micro-organisms in neutrophils, eosinophils, monocytes and macrophages. The leukocyte NADPH oxidase is composed of five subunits, of which the enzymatic component is gp91phox, also called Nox2. This protein is encoded by the CYBB gene on the X chromosome. Mutations in this gene are found in about 70% of all CGD patients in Europe and in about 20% in countries with a high ratio of parental consanguinity. This article lists all mutations identified in CYBB and should therefore help in genetic counseling of X-CGD patients' families. Moreover, apparently benign polymorphisms in CYBB are also given, which should facilitate the recognition of disease-causing mutations. In addition, we also include some mutations in G6PD, the gene on the X chromosome that encodes glucose-6-phosphate dehydrogenase, because inactivity of this enzyme may lead to shortage of NADPH and thus to insufficient activity of NADPH oxidase. Severe G6PD deficiency can induce CGD-like symptoms.