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| Vol. 21, No. 20 |
| November 1, 1999 |
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Chromosome Deletion that Causes DiGeorge Syndrome is Found in Mice by B. J. Almond Baylor College of Medicine A mouse model for studying a congenital heart disease has provided clues about the genetic cause and a possible way to prevent the disorder. Researchers at Baylor College of Medicine and Howard Hughes Medical Institute (HHMI) created the mouse model to study DiGeorge syndrome, a genetic disorder that causes potentially lethal heart defects. They identified the deleted portion of the chromosome that produces the defects and found that duplicating this chromosome region can prevent the defects. Their study was reported in the Sept. 23 issue of the scientific journal Nature. DiGeorge syndrome occurs in one of every 4,000 babies. About 8 percent of patients with the disorder die from a defect in the aorta that prevents the lower part of the body from receiving oxygenated blood. The defect must be surgically repaired during the first few days of life. Other patients with DiGeorge syndrome might develop related heart problems that require surgery within the first several months, facial abnormalities, mild retardation and psychiatric problems. In humans, the disorder has been traced to a missing portion of chromosome 22. This chromosome deletion, known as del22q11, spans approximately 25 genes, although which one of those missing genes causes the syndrome remains unknown. The deletion occurs on only one of the two chromosomes 22; the other chromosome in the pair is normal. Dr. Antonio Baldini, assistant professor of pediatrics and associate professor of molecular and human genetics at Baylor and an associate in cardiology at Texas Children's Hospital, led the research team that developed the mouse model to study DiGeorge syndrome. He found a region on mouse chromosome 16 that is similar in size and gene content to the chromosome deletion in humans. When that region was deleted on one of the two chromosomes 16, the mice developed heart defects shortly after 10 days of embryonic development, which corresponds to 27 to 29 days in humans. This confirmed that the chromosome deletion is responsible for the heart defects in DiGeorge syndrome and provided evidence of the time at which the defects occur. But the research yielded a surprise to Dr. Baldini and colleagues: When mice with the chromosome deletion were bred with mice that had a duplication, or extra copy, of the same portion of chromosome 16, no heart defects developed. "This discovery might be useful in developing a preventive treatment for these heart defects, but much more research will be needed before such an application could be designed for humans," Dr. Baldini says. "The most important thing is that we now have a model on which we can test preventive strategies suitable to humans." Because the deletion on mouse chromosome 16 spans only 15 genes, the study also revealed that the search for the specific genes that cause the problem in humans can he narrowed from 25 to 15. "The other 10 genes in the human chromosome deletion apparently don't cause congenital heart disease," Dr. Baldini says. Other members of the research team in Baylor's department of molecular and human genetics were Dr. Allan Bradley, also an HHMI investigator, Dr. Elizabeth A. Lindsay, Dr. Annalisa Botta, Vesna Jurecic, Sandra Carattini-Rivera, and Yin-Chai Cheah. Dr. Howard M. Rosenblatt in the department of pediatrics also collaborated on the study, which was funded by the National Heart, Lung and Blood Institute.
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