Chronic granulomatous disease, the McLeod phenotype and the contiguous gene deletion syndrome-a review

Abstract

Chronic Granulomatous Disease (CGD), a disorder of the NADPH oxidase system, results in phagocyte functional defects and subsequent infections with bacterial and fungal pathogens (such as Aspergillus species and Candida albicans). Deletions and missense, frameshift, or nonsense mutations in the gp91phox gene (also termed CYBB), located in the Xp21.1 region of the X chromosome, are associated with the most common form of CGD. When larger X-chromosomal deletions occur, including the XK gene deletion, a so-called "Contiguous Gene Deletion Syndrome" may result. The contiguous gene deletion syndrome is known to associate the Kell phenotype/McLeod syndrome with diseases such as X-linked chronic granulomatous disease, Duchenne muscular dystrophy, and X-linked retinitis pigmentosa. These patients are often complicated and management requires special attention to the various facets of the syndrome.

Figure 1

XK and CYBB are neighboring genes. A. Idiogram of human chromosome X at 550 banding resolution. The bar indicates the location XK and CYBB genes and is expanded below to show the genomic region. B. Genomic context of Xp21.1. The region of chromosome X from 37,500 to 37,700 K is shown. Arrows indicate the location of the XK and CYBB genes. Numbering is based upon GenBank accession number NC_000023.10.

Figure 2

Complicating conditions often seen in the Contiguous gene deletion syndrome associated with chronic granulomatous disease.

Figure 3

Structure of the XK and Kell proteins.