The gene that causes neurofibromatosis, a disfiguring disease once thought to be suffered by John Merrick, the Elephant Man, has been discovered by two teams of American researchers, the scientists announced yesterday.
An estimated 100,000 Americans live with the disease, known as NF, making it nearly as common as cystic fibrosis, the most frequently inherited illness.
In NF, damage to the gene causes uncontrolled growth of certain types of nerve cells, leading to the formation of frequently painful non-cancerous tumors all over the body. The tumors increase in size and number with age, and, at their worst, can disrupt bone formation, causing serious disfigurement.
The tumors also can cause neurological defects, such as deafness, blindness, seizures and learning disabilities; in about 5 percent of the patients, the tumors turn into life-threatening cancers.
"Now that the gene is in hand, we should be able to figure out its normal function, and work toward a useful treatment," said Francis S. Collins, a geneticist at the University of Michigan Medical Center and leader of one research group that found the gene.
Raymond L. White of the University of Utah School of Medicine led the other team. Both groups were funded by the Howard Hughes Medical Institute in Bethesda. Collins's study is reported in today's issue of Science magazine; White's in today's issue of Cell.
"It is a very, very important first step to identifying the fundamental process in this disorder," said Roger J. Porter, deputy director of the National Institute of Neurological Disorders and Stroke.
No one understands what the NF gene controls, but it appears to act like a brake on cell division, Collins said. Similar growth-controlling genes have been associated with certain kinds of cancer; when they are damaged or lost through some genetic accident, the cell becomes malignant. Collins said inactivation of the NF gene may play a role starting some cancers, including brain cancer.
In the next few months, both research groups expect to identify the protein that is made by the NF gene. Once they understand how the protein controls cell growth, it may be possible to find a drug that mimics that function and, essentially, turn off the disease. That, however, is probably years away, the scientists said.
Currently, surgery is the only treat- ment for NF, and that is limited to re- moving tumors that are damaging vital tissues, such as blood vessels, nerves and organs.
Even if a new therapy does not come quickly, the gene's discovery is expected to lead to a diagnostic test which would help identify the disease in very young children, Collins said.
Merrick, the 19th-century Englishman characterized as the Elephant Man in play and film, suffered a severely disfiguring disorder once thought to be neurofibromatosis.
Since 1986, scientists have believed that Merrick's disfigurement was actually caused by the Proteus syndrome, a very rare genetic disorder completely unrelated to NF that causes asymmetric growth of arms and legs, changes in head size, and many different kinds of non-cancerous tumors in the skin.
While the association with Merrick helped raise public awareness of NF, and helped raise research funding for the National Neurofibromatosis Foundation Inc.,
in New York, it has had a frightening ef- fect on many NF patients who feared they would develop symptoms as bad as Merrick's.
And, like Merrick, many NF patients have been shunned because of their deformities.
"Neurofibromatosis has caused me social isolation," said Porter Colley, who has NF tumors all over her body and appeared at yesterday's news conference. "I have been called Mrs. Merrick."