Gene find to guide search for cure.

Byline: Diane Dietz The Register-Guard

Genetic researchers say they've made a particularly interesting leap toward understanding Fanconi anemia.

Researchers identified two more genes - in addition to 11 found earlier - associated with the rare genetic disease that kills the afflicted by early adulthood, and some much sooner.

These new genes are remarkable: They're older in an evolutionary sense than other genes. They're allowing researchers to see relationships between genes and proteins, and the answers may help them figure out what causes the inherited condition. And that's got them hyped.

"We're seeing evidence of a real machine that takes care of certain specific lesions in DNA," said Maureen Hoatlin, co-investigator with 13 others in a study that was published Monday in the online version of Nature Genetics. "We're getting down, now, to the central mechanism."

Fanconi's anemia strikes only one child in 300,000, but the disease has a high profile in Eugene because University of Oregon President Dave Frohnmayer lost two daughters to the illness. A third, Amy, is surviving her disease.

A tantalizing aspect of the new discovery is that the Fanconi anemia genes are associated with the repair of DNA, which is the code in a cell's nucleus that guides its replication.

A malfunctioning DNA repair mechanism also may be related to ovarian cancer, pancreatic cancer and leukemia.

"(The genes) are major players in a fundamental sense in protecting the integrity of the human cell from things like cancer," Frohnmayer said Monday. "It puts us squarely in the mainstream of major research."

The groundbreaking research was funded in part by Eugene-based Fanconi Anemia Research Fund, which was created 16 years ago by Frohnmayer and his wife, Lynn. The foundation raises about $1.4 million a year, and 94 percent goes to research and help for children with the anemia.

The discovery doesn't mean scientists can go immediately to the lab and whip up a retro-viral medicine for Fanconi patients missing the key genes - or make a drug that will help their existing genes function better.

Still, it's pretty exciting, Hoatlin said, "because for years people didn't have any idea what these (gene-produced) proteins were doing and it was frustrating," she said.

"Now there's a very clear path for us to follow, very clear experiments to do, very obvious questions to ask. This puts us in a position in Fanconi anemia research that we haven't been before."

In the meantime, the 500 U.S. children with the anemia will have to wait and hope that they survive until a therapy can be found.

Many will get leukemia and will have to endure a bone marrow transplant to try for renewed life. And those survivors are highly susceptible to cancers of the head and neck.

The anemia has made 18-year-old Amy Frohnmayer tired from time to time, but she said she feels very fortunate.

Her eldest sister, Kirsten, died eight years ago at age 24. Another older sister, Katie, died 14 years ago at age 12.

Amy said she feels healthy and strong. Her dad said she is a happy kid. She's headed for Stanford University this fall to study psychology, international relations and/or Spanish.

She's already had a hard-learned lesson in genetics, and she was thrilled to hear about the newest research.

"It's extremely exciting. Every single discovery is so important. It's definitely cumulative," she said. "It's giving so much hope for so many patients all around the world."

FANCONI ANEMIA

Cause: It's a recessive disorder, meaning that when both parents carry a defect in the same gene, there's a 1-in-4 chance their child will be born with it. The disease usually emerges between ages 3 and 12.

Effects: Fanconi anemia causes bone marrow failure. The marrow slowly stops making red and white blood cells and platelets. Many sufferers develop acute myelogenous leukemia. Older patients may develop other cancers.

Learn more: Call the Fanconi Anemia Research Fund, 687-4658. Or on the Web: www.fanconi.org

CAPTION(S):

Amy Frohnmayer, daughter of Dave and Lynn Frohnmayer, says she is thrilled about the findings on Fanconi anemia, a disease she bears.