January 26, 2001

MGH researchers have identified the gene that causes familial dysautonomia (FD), a degenerative neurological disorder found in the Ashkenazi Jewish population, whose ancestors originated in Eastern Europe. One in 30 Ashkenazi Jews carries the FD gene, and approximately one in 3,600 individuals is affected. In FD, the autonomic and sensory nervous systems fail to develop fully, resulting in a host of complications ranging from difficulty in swallowing and feeding (in infants) and problems controlling heart rate and blood pressure. Sixty percent of all infants with FD require tube feedings, and many of those affected are born without taste buds or the ability to produce tears. Despite advances in medical treatment, only about 50 percent of patients live to be 30 years old.

The MGH team, under the direction of James F. Gusella, PhD (right), director of the MGH Molecular Neurogenetics Unit, has shown that mutations in a gene named IKBKAP cause FD. The findings will appear in the March issue of the American Journal of Human Genetics. The immediate result of this discovery will be the ability to do carrier testing in the Jewish population.

"While genetic testing for at-risk families has been going on for years, our discovery now will permit anyone in the general Jewish population to have carrier testing," says Gusella. In addition to discovering the mutations that can cause FD, Gusella's team has shown that the expression of the mutant gene in FD patients varies depending on what cell types are examined.

"The fact that we see normal protein expressed in some patient cell types, despite the presence of the mutation, is unusual and important. By investigating this underlying mechanism, we may learn how to increase the amount of normal protein made in nerve cells, which could lead to a treatment for the progressive neuronal loss seen in FD," says Susan A. Slaugenhaupt, PhD, also of the MGH Molecular Neurogenetics Unit, and the other principal author of the paper.

Gusella, Slaugenhaupt and their team have been studying FD for more than 10 years, and the successful prenatal testing that has resulted in the birth of 69 healthy babies is the direct result of their earlier discoveries. The team has been supported by the Dysautonomia Foundation for 10 years and has also received support from the National Institutes of Health, the Israeli Science Ministry and the US-Israel Binational Science Foundation.