Gene for DiGeorge Syndrome discovered

HOUSTON--(Feb. 22, 2001)--The gene responsible for DiGeorge Syndrome, a disorder that is one of the most common genetic causes of congenital heart defects, has been discovered by Baylor College of Medicine researchers.

Using a mouse model, Dr. Antonio Baldini, an associate professor of pediatric cardiology and molecular and human genetics at Baylor, and his team found that Tbx1 is the genetic cause of DiGeorge Syndrome. The discovery is reported in the March 1 issue of the scientific journal Nature.

"Since this gene is a transcription factor that regulates other genes, we think that by studying what it controls, we should be able to get a handle on a number of birth defects," he said.

DiGeorge Syndrome, which affects one in 4,000 babies, produces a range of symptoms, including structural heart defects and the absence of the thymus and parathyroid glands. Some infants must have corrective heart surgery in the first days of life. Infections, seizures and facial abnormalities, especially of the jaw, also are seen.

Many of those diagnosed with DiGeorge Syndrome suffer from borderline mental retardation, although it remains to be demonstrated whether the deletion of Tbx1 can also cause this symptom.

Previously, the disorder had been linked to a missing portion of the human chromosome 22. In earlier research, the Baylor team reproduced the chromosome deletion, known as del22q11, in laboratory mice. The earlier research provided the basis for the current discovery. Baldini's team was able to identify the gene using chromosome engineering technologies developed at Baylor and data from the human genome sequencing project.

"Now, that we know what the gene is, we can look at patient populations to see if they carry mutations in that gene," Baldini said. "This could help with diagnosis and possible prevention strategies in the future."

Other members of the research team include Elizabeth A. Lindsay, Francesca Vitelli, Hong Su, Masae Morishima, Tuong Huynh and Tiziano Pramparo of Baylor; Vesna Jurecic of the University of Miami School of Medicine; George Ogunrinu of the University of Texas, M.D. Anderson Cancer Center; Helen F. Sutherland and Peter J. Scambler of the Institute of Child Health in London; and Allan Bradley, formerly of Baylor and now director of the Sanger Centre in Cambridge.