OHSU Researchers Help Unlock Genetic Secrets of "Overheating" Disorder

08/02/99    Portland, Ore.

Discovery Published in Current Issue of Nature Genetics.

When the mercury rises, the human body counteracts with it's own personal air conditioner in the form of perspiration. But hot weather can prove dangerous or even deadly for some people born with a genetic disease called hypohidrotic ectodermal dysplasia. The disorder blocks the formation of sweat glands. Their absence could cause a person to overheat in high temperatures. Patients display additional symptoms such as malformed or missing teeth, dry skin and sparse hair growth.

Now thanks in part to research at Oregon Health Sciences University, investigators are unlocking the secrets of HED. OHSU's Jon Zonana, M.D. and Betsy Ferguson, Ph.D., of OHSU's department of molecular and medical genetics, are on a team that found the latest piece in the puzzle. The team located a mutated gene called dl on the human chromosome-two, which contributes in part to the disorder. Their findings will be published in the August edition of Nature Genetics.

To locate the gene, scientists at OHSU and the Baylor College of Medicine joined forces. They started on a smaller scale, studying the DNA sequence information of downless mice, named for their sparseness of hair. Baylor researchers were able to track down the aberrant gene in the mice. OHSU researchers then used this information to find the equivalent defect in humans. A group of 12 families were involved in this gene mapping investigation.

This finding follows the discovery of a different gene on the X-chromosome that also produces HED symptoms. In 1996, researchers located a gene named ED1 on the X-chromosome of humans. That gene causes HED symptoms to surface in males and a small percentage of females. Women are less susceptible to the effects of the mutated gene on the X-linked chromosome because they are born with two X-chromosomes. This allows for the defective gene to be masked by a normal partner gene. In contrast, men have only one X-chromosome making them more susceptible. Despite this revelation, doctors were still unable to identify the gene responsible for HED in some male and female patients, until now.

Both discoveries lead to a better understanding of the disorder. In addition, there are a number of clinical benefits. Doctors will now be able to better determine the chances of the genetic disease showing up in the children of parents with a history of HED. The research may also lead to better therapies for treating patients.

However, the search for answers is far from over. Researchers are now looking for yet another gene that can cause hypohidrotic ectodermal dysplasia-like symptoms. "It's a big attempt to determine how humans form and the problems that can occur," says Zonana. "This just adds one more molecule we can try and fit into the puzzle."

Research team members from the Baylor College of Medicine include Paul Overbeek, M.D. and Denis Headon.

Jon Zonana, M.D., professor of molecular and medical genetics, School of Medicine

Betsy Ferguson, Ph.D., Assistant professor of molecular and medical genetics, SM

Note to editor: Interviews with Dr. Zonana can be arranged by contacting Jim Newman at (503) 494-8231.