Scientists said yesterday that they have discovered the gene behind the most common type of inherited mental retardation, a significant advance in understanding not only a mental defect but also the genes that help fashion human intelligence.
In its mutant form, the gene causes a baffling kind of retardation, fragile X syndrome, that is proving to be more widespread the more adept experts have become at detecting and diagnosing it.
With the discovery of the gene, doctors should now be able to diagnose the disease unequivocally. That new skill will allow physicians to perform prenatal diagnoses in families with a high incidence of fragile X syndrome.
The discovery will also enable researchers to identify syndrome patients whose retardation or behavioral difficulties had been attributed to conditions such as autism or a lack of oxygen during birth.
Fragile X syndrome occurs in about 1 in 1,000 males and 1 in 2,500 females.
As a cause of mental retardation, this is second only to Down's syndrome, which affects 1 in 600 babies but is not hereditary.
The severity of fragile X syndrome ranges from mild learning disabilities to retardation so severe that the afflicted can barely talk or function.
Although no treatments currently exist for the syndrome, scientists say that identifying the gene will enable them to study how it operates in normal brain cells to influence intelligence, and why flaws in it cause retardation or related types of mental disorders.
"Fragile X has been a puzzling disorder, and there have been so many theories about the disease, all of which have been almost impossible to test," said Dr. Stephen T. Warren of Emory University School of Medicine in Atlanta, the main author of the new report, which is appearing in tomorrow's issue of the journal Cell.
"Now that we've got the gene, we can start asking a lot of exciting questions and doing a lot of straightforward research."
Dr. Warren also said that he and his colleagues have a few clues to the shape and function of the protein produced by the fragile X syndrome gene.
The protein has several properties unlike any yet observed in other human proteins, suggesting that it might react with neighboring proteins in brain cells in an entirely novel manner.
The quest for the fragile X gene has been long and fevered, involving the efforts of laboratories worldwide and resulting in a stream of papers recently as researchers crept ever closer to their quarry.
The new paper is the denouement of that effort, and others in the field of human genetics said it represented a big jump forward.
"Fragile X has presented a very big problem in genetic counseling, and it's been hard to say whether a person carries the gene or not," said Dr. W. Roy Breg, a professor of human genetics and pediatrics at Yale University School of Medicine.
"To have the gene itself, rather than having to rely on other markers, will be an enormous help," Dr. Breg said.
Parents who are informed that their fetus has the syndrome may choose abortion, Dr. Warren said; but if they proceed with the pregnancy, they can be informed about the possible spectrum of symptoms.
Adults found to be carrying the defect may choose not to risk having children in the first place.
Dr. David H. Ledbetter, a professor of genetics at Baylor College of Medicine in Houston, said the new paper, together with announcements last week in the journal Science that scientists had found pieces of the gene, have thrown the field wide open.
"The whole field has leaped forward rapidly, after years of not much visible progress," he said.