Chronic granulomatous disease. Molecular genetics

Area of Science:

• Immunology
• Genetics
• Molecular Biology

Background:

• Chronic granulomatous disease (CGD) is an inherited disorder affecting microbial killing.
• Phagocytic cells fail to produce superoxide due to NADPH-oxidase defects.
• The genetic basis of X-linked CGD (X-CGD) was investigated using a genetic approach.

Purpose of the Study:

• Identify the gene responsible for X-CGD.
• Characterize the protein product of the X-CGD gene.
• Explain the absence of phagocyte cytochrome b in X-CGD patients.

Main Methods:

• Gene mapping to Xp21.1.
• Identification of a phagocyte-specific RNA transcript.
• Use of antisera against the predicted protein product.
• Biochemical purification of phagocyte cytochrome b.

Main Results:

• The X-CGD gene was mapped to Xp21.1.
• A deficient phagocyte-specific RNA transcript was found in X-CGD patients.
• The X-CGD gene product is a 90-kD membrane glycoprotein, part of the phagocyte cytochrome b.
• Both 90-kD and 22-kD subunits of cytochrome b are absent in X-CGD.

Conclusions:

• The genetic deficiency of the larger subunit explains the absence of both cytochrome b subunits.
• Further characterization of the smaller subunit is needed for a complete understanding.
• Cloned X-CGD reagents may aid prenatal diagnosis and gene therapy.