Phagocytes from X-linked chronic granulomatous disease (X-CGD) patients are deficient in their ability to generate superoxide because of a defective gene that encodes a heavy chain of cytochrome b, a critical component in the superoxide-generating pathway.
Somatic cell hybridization was performed between the monocytes from the affected boy in this family with monocytes from either a cytochrome b-negative male patient with X-linked chronic granulomatous disease or a cytochrome b-positive male patient with the classic autosomal form of this disease.
Cytochrome b-245 is the only clearly defined component of this oxidase system and its absence provides the molecular basis of X-linked chronic granulomatous disease (CGD), in which a profound predisposition to infection results from complete failure of this respiratory burst.
Variant X-linked chronic granulomatous disease (CGD) is characterised by a decreased but still measurable respiratory burst and cytochrome b content of phagocytes resulting in a clinically milder form of the disease.
Missense mutations in the gp91-phox gene encoding cytochrome b558 in patients with cytochrome b positive and negative X-linked chronic granulomatous disease.
Since the genetic mutation responsible for this type of CGD results in the absence of cytochrome b-558 in PMNs, fibroblasts should be affected in the same way if both cytochrome species were identical.
We report here two atypical cases of X-linked CGD patients (first cousins) in which cytochrome b(558) is present at a normal level but is not functional (X91+).
A newly recognized point mutation in the cytochrome b558 heavy chain gene replacing alanine57 by glutamic acid, in a patient with cytochrome b positive X-linked chronic granulomatous disease.
X-linked chronic granulomatous disease (X-CGD) is a primary immunodeficiency disease of phagocytes caused by mutations in the cytochrome b(558)β (CYBB) gene.
In association with these functional changes, we observed an increase in cellular contents of phagocyte cytochrome b (a critical component of the superoxide-producing oxidase) and immunoreactive cytochrome b heavy chain (the product of the gene that is defective in X-linked chronic granulomatous disease).