This fall, people with a 50/50 chance of developing Huntington's Disease will be able to have their blood tested to determine whether or not they will get the progressively fatal disorder. The test can also be done in utero.
This new test is the latest in a series of expanding gene probes that are rapidly changing the capabilities of genetic counseling and prenatal screening in the United States.
For the first time, this sophisticated genetic technology is allowing scientists to identify before birth such diseases as muscular dystrophy, cystic fibrosis and a rare but fatal eye cancer known as retinoblastoma.
Unlike past genetic screening which relied upon looking for the far less accurate biochemical markers for diseases, researchers can now hunt and identify the actual gene that causes the illness.
"These technologies are allowing great precision in an area of ambiguity," says Dr. C. Thomas Caskey, director of the Robert J. Kleberg Center for Human Genetics at Baylor College of Medicine in Houston. "They allow families to make accurate decisions."
These and other new findings were reported here last week at a special course on genetics, sponsored by the March of Dimes, Johns Hopkins University and the Jackson Laboratory in Bar Harbor.
Scientists have long recognized that contracting a serious disease is at least partly determined by the deoxyribonucleic acid (DNA) -- the genetic blueprint -- passed down in families from generation to generation.
But only since 1978 has it been possible to identify and clone -- or genetically copy -- specific genes that cause these diseases.
To do this, researchers at some key institutions throughout the country employ special DNA probes, or molecular-sized detectors, tailor-made to identify specific genes. A gene is a portion of DNA.
The use of DNA probes for diseases such as sickle cell anemia now makes it possible to identify carriers of the disease. It also enables doctors to determine whether an unborn child will be affected by the disease.
Although biochemical tests are now available for some 100 genetic diseases, this second generation of genetic tests is "far more accurate and more specific," said Dr. Stylianos E. Antonarakis of the genetics unit at the Johns Hopkins Medical Institutions.
The biochemical tests look in the blood or amniotic fluid for substances produced as a result of the disease, while the new genetic tests identify the gene -- or a marker for the gene -- itself.
As an example of the progress of these DNA probes, Dr. Haig Kazazian, Jr. -- a pediatrics professor at Johns Hopkins -- says, "A year ago we knew the gene for Huntington's was in the U.S. Now we know its in D.C. Next, we'll know whether it's located on Constitution or Independence Avenue."
The goal of developing more of these highly specific probes is to one day identify and treat many other common illnesses such as heart disease and cancer very early. Theoretically, genetic probes could someday identify at birth those people who are susceptible to heart attacks or breast cancer. People at risk could be medically monitored and take other precautions to minimize development of the disease.
Approximately 15 genetic diseases can now be identified with greater than 90 percent accuracy using this new DNA technology, scientists reported at the Bar Harbor conference. Only a handful of medical centers are using the DNA probes, including Johns Hopkins, Baylor College of Medicine and Children's Hospital in Boston.
The diseases that can now be diagnosed are blood disorders such as sickle cell anemia, hemophilia and thalassemia. Other illnesses include Duchenne's and Becker's Muscular Dystrophy -- diseases that account for an estimated 95 percent of all childhood muscular dystrophy cases in the United States; Lesch-Nyhan disease, a gradually fatal disorder that causes severe mental retardation and self-mutilation; cystic fibrosis and adult polycystic kidney disease which accounts for one quarter to one third of all kidney failure in the United States today.
Huntington's disease is the latest addition to this growing list of genetic disorders that can be identified through DNA probes. A gradually degenerative nerve and brain disease, Huntington's affects about 25,000 people in the United States.
The disease, which affects men and women equally, can be caused by just one aberrant gene -- unlike some genetic diseases which are caused by changes in several genes.
People who develop Huntington's disease gradually lose control of their muscles and also develop dementia. What makes this illness particularly difficult is that its symptoms do not appear until age 35 or later. Those at risk for the disease -- some 100,000 Americans who are the son or daughter of a Huntington's patient -- have no way of knowing if they will also develop the illness. If they do carry the gene, they have a 50/50 chance of passing it on to their own children.
The introduction of this new test will finally change this state of limbo for Huntington's families.
"At least three centers will be initiating presymptomatic testing of Huntington's families on Sept. 1," said Dr. Joe Martin, chief of neurology at Massachusetts General Hospital in Boston. In addition to Massachusetts General, Johns Hopkins and Columbia-Presbyterian Medical Center in New York will be offering the new test, Martin said.
Early testing will be limited to families at these three institutions who have already been participating in pilot programs sponsored by the National Institute of Neurologic and Communicative Disorders and Stroke, he said.
"My guess," Martin said "is that over the next 12 months, several other centers will also come on line and offer the test." Among the centers that have expressed interest in offering Huntington's test are the Baylor College of Medicine in Houston, the University of Michigan and the University of Oregon.
But the DNA test is not without problems. This is one of the first medical tests that will be able to tell an outwardly healthy person that they "have a 90 percent chance of carrying a gene that will produce a fatal disease within a number of years," Martin said. No one is certain what effect that news will have on people. Parents who discover their unborn child has a serious disease may opt to terminate the pregnancy.
But in addition to the potential for bad news, this new Huntington's test will also be able to tell people with 90 percent accuracy that they do not carry the gene. That means that neither they, nor their children will be affected.
Surveys of Huntington's disease families have found that "two-thirds of people indicate they would like to be tested," Martin said. Those who are tested will have access to special psychological counseling services.
Despite these ethical dilemmas, researchers predict that these new tools will be of enormous help in early detection -- and, someday, cure.
One of the most striking examples is with the eye cancer retinoblastoma, a rare disease that afflicts children by age five. Unless the disease is caught very early, the only treatment is for the children's eyes to be removed.
Ludwig Institute's Dr. Webster Cavenee reported that he and his colleagues were able to take a sample of umbilical cord blood from a newborn baby in Sweden and test it for retinoblastoma.
The baby's mother had the gene for the disease. But doctors were uncertain if the child would also be affected. An older half-brother had no evidence of the disease.
The only way to detect retinoblastoma in infants is to conduct an extensive hour long eye exam under general anesthesia. This is very risky for newborns, Cavenee said, and is generally postponed in infants under three months of age. But by that time, it is often too late to save the child's eyesight.
In this case, however, doctors air-expressed blood from the baby to Cavenee's laboratory where it was tested with the DNA probe for retinoblastoma. The test showed that the child had the disease.
With that certainty, the doctors took the risk of performing the extensive eye exam on the then five-day-old child. They found several early tumors in each eye. The tumors were halted with irradiation and, today, at three years of age, the child still has his sight.
"Those are the kinds of things we are now able to do," Cavenee said. Resources: If you have an immediate relative who has been afflicted with muscular dystrophy, cystic fibrosis, sickle cell anemia, thalessemia or hemophilia and you are considering having a child, you can find out more about genetic screening from the Johns Hopkins genetics unit by calling (301) 955-3091.