Nature 327, 720 - 721 (25 June 1987); doi:

The X-linked chronic granulomatous disease gene codes for the -chain of cytochrome b_-245

Carmel Teahan, Peter Rowe, Peter Parker^*, Nick Totty^* & Anthony W. Segal^†

Department of Medicine, Faculty of Clinical Sciences, University College London, London WC1E 6JJ, UK
^* Ludwig Institute for Cancer Research, Imperial Cancer Research Fund, London WC2A3PX, UK
^† To whom correspondence should be addressed.

Chronic granulomatous disease (CGD) is a rare inherited disorder associated with a profound predisposition to infection due to the lack of a microbicidal oxidase system in the phagocytes of these patients¹. This syndrome is most commonly inherited through a defect on the X chromosome and the only clearly defined component of the oxidase system, the very unusual cytochrome b (b _-245), has been shown to be missing from the cells of these patients^2,3. This cytochrome is a heterodimer composed of an -chain of relative molecular mass (M _r) 23,000 (23K) and a 76–92K -chain; neither are detectable in neutrophils from X-linked CGD subjects. The defective X-CGD gene has recently been cloned⁴ by 'reverse genetics'⁵ but the protein predicted from the proposed complementary DNA sequence was not identified. We have purified the -chain of the cytochrome and sequenced 43 amino acids from the N terminus. Almost complete homology was obtained between this sequence and that of the complementary nucleotides 19–147 of the sequence of the X-CGD gene, originally designated as a non-coding region.