Navigate Exhibit by Clicking hereDiagnosing and Treating Genetic Diseases
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  Chronic Granulomatous Disease (CGD)

The most common white blood cells -- neutrophils -- combat infections by producing germ-killing substances: hydrogen peroxide and bleach. People with CGD have genetic mutations that prevent the blood cells from making the proteins necessary for this process. As a result, infections that most of us easily fight are life-threatening to people with CGD.

Two-thirds of people with CGD are males who inherited the disease on the X-chromosome from their mother (males have an X-chromosome from their mother and a Y-chromosome from their father). In these cases, CGD is called an X-linked genetic disease. In general, females do not have problems when one of their X-chromosomes carries the X-linked CGD mutation. Non-X-linked forms of CGD affect both boys and girls.  
Hereditary Diagram

Heredity  diagram

From gene to protein

In 1985, Dr. Uta Francke at Yale University and her colleagues described a man with X-linked CGD who also had three other X-linked diseases. When his X-chromosome was examined, there was a small piece missing, indicating where on the X-chromosome all four of these disease-linked genes could be found.

In 1987, Dr. Stuart Orkin in the Howard Hughes Medical Institute at Harvard University and his colleagues used this information to isolate the X-linked CGD gene. Since then, three other CGD genes have been found on other chromosomes, making CGD four distinct genetic disorders. 

Daily doses of antibiotics reduce infections in people with CGD. Injections of interferon gamma, a potent immune system hormone, also reduce infections in these patients. Scientists used recombinant DNA technology to make useful amounts of this hormone from bacteria. While these treatments are not a cure for CGD, they have improved the outlook for people with CGD.

A gene therapy trial to treat a non-X-linked form of CGD started at NIH in July 1995. Immature white blood cells were purified from the blood of a person with CGD. The cells were treated with the normal gene, and put back into the same person. Five people with CGD were treated this way. Although only some corrected cells stayed in the bloodstream for several months, this effort represented an important step in developing gene therapy for CGD. This photo shows white blood cells from one of the people who received gene therapy. The dark cell has been corrected by the gene treatment. For more on gene therapy, see this page.
  Photomicrograph of NBT test - Courtesy of Dr. Harry L. Malech and Dr. Douglas Kuhns, National Institute of Allergy and Infectious Diseases
Photograph of NBT test. Courtesy of Dr. Harry L. Malech and Dr. Douglas Kuhns, National Institute of Allergy & Infectious Diseases

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Revolution in Progress: Human Genetics and Medical Research/
National Institutes of Health