A 10-year-old Utah boy died recently in front of his class after being scolded. His death, though tragic, wasn't surprising to his parents, who had lost two other of their eight children to the mysterious cardiac arrhythmia, known as the long QT syndrome or sudden death.
By studying the family's bloodlines, University of Utah researchers have been able to pinpoint the marker for the mutant gene that passes along the syndrome.The discovery is remarkable because 500,000 children and young adults die annually when their heart beats so furiously it can't pump blood to the brain. Although effective treatments exist, it's difficult to predict who is at risk. Surprisingly, the first symptom of the disease can often be death.
Mark Keating, a University of Utah cardiologist and molecular geneticist, has been tracing the gene since October 1989. Another researcher, Dr. Mike Vincent at LDS Hospital, has been studying the family for 17 years.
A gene search can be tedious, similar to finding a house somewhere on Earth without a map, Keating said. Researchers examined 245 probes - the equivalent of 60 percent of the total DNA material in a human - before finding the specific mutation. "We weren't that lucky. It's very much like looking under stones and saying, `Well, it's not there,' and keep looking."
A paper announcing the discovery, written by Keating, Vincent and other Utah researchers, has been published in the May 3 edition of Science.
With the knowledge of this marker confirming the disease is hereditary, researchers can examine a newborn child and determine whether the child has a defective gene, Keating said. The marker is located on chromosome 11, right on top of the Harvey-ras gene. Mutations of the ras gene are known to contribute to the growth of several cancers.
While the ras gene might not be the actual site of the defect that causes long QT syndrome, it is at least very close, Keating said. Since he identified the marker last fall, Keating has looked at six other families with the genetic disease, and the pattern holds.
Now that the gene marker has been identified, researchers need to study the protein it encodes to understand why the mutation occurs. Then, hopefully through genetic therapy or medication, the syndrome could be prevented or controlled.
The Utah announcement is just another in a series of dramatic gene discoveries in what Keating refers to as the big-problem diseases. "The little pieces of the puzzle are coming together."