OHSU Researchers Successfully Identify and Clone Fanconi Anemia Gene

02/15/01    Portland, Ore.

Discovery Provides New Insight Into the Causes of and Possible Cures for the Fatal Genetic Disorder

It's not as common as cancer or Alzheimer's disease, but for many Oregonians, Fanconi anemia (FA) hits close to home. During the last 10 years one of the state's most prominent families has lost two members to the genetic disorder. In 1991 12-year-old Katie Frohnmayer died from complications caused by the disease, and 24-year-old Kirsten Frohnmayer died in 1997, two years after receiving a bone marrow transplant. Both are daughters of David Frohnmayer, president of the University of Oregon, and his wife Lynn.

This week researchers at Oregon Health Sciences University are pleased to announce they have identified and cloned a key FA gene. OHSU researchers believe the discovery could provide important clues to the cause and cure of FA. Markus Grompe, M.D., a professor of molecular and medical genetics, and pediatrics in OHSU's School of Medicine, Robb Moses, M.D., chairman of the Department of Molecular and Medical Genetics, and geneticist Susan Olson, Ph.D., directed the project at OHSU. Research was conducted in collaboration with the Dana-Farber Cancer Institute, Harvard Medical School, Boston, Mass; and The Hospital for Sick Children, Toronto, Ontario. Conclusions are printed in the Feb. 16 edition of Molecular Cell.

FA is associated with multiple, severe birth defects as well as a predisposition to cancer. FANCD2 is one of at least eight genes responsible for FA. So far five other genes have been cloned. By cloning the FANCD2 gene, researchers can now closely study the complex systems involved in the disease. OHSU scientists also believe FANCD2 will help prove one of the theories about FA. Grompe and his colleagues theorize that the disease is related to a disturbance in the cell's ability to repair certain types of DNA damage. Based on their research, it appears that FANCD2 regulates this repair system and is turned on by the other FA genes when they are working properly. When these genes are not working properly and FANCD2 is not activated to allow for genetic repair, FA develops and the damage to cellular genes causes cancer. The research team theorizes that if a compound can be identified that activates the FANCD2 gene, damage will be repaired and the disease may not surface.

"Another exciting aspect of the FANCD2 gene is that unlike other FA genes it also can be found in other organisms, including flies and plants. This leads us to believe that it may be the key gene that can be traced to the origins of FA, before it ever surfaced in the human race," explains Grompe.

In addition to cloning the FANCD2 gene, OHSU scientists confirmed a likely relationship between this FA gene and another cancer related gene, called BRCA1, that plays a role in the development of familial breast cancer. The scientists showed that the two genes act together to protect cells against DNA damage and tumors.

"While this is exciting news, we weren't entirely surprised by this finding, said Grompe. "Fanconi anemia patients are very susceptible to cancer. We believe that the FANCD2 gene could play a role in the development of some forms of cancer, making both genes part of very important disease pathways and targets for future research."

The Frohnmayers and the Fanconi Anemia Research Fund, which the family organized in 1989, have helped OHSU and several other institutions around the world to further the understanding of FA. The early stages of OHSU's research were supported by the fund. The National Heart, Lung and Blood Institute, a component of the National Institutes of Health, provided additional funding.

"We believe this is the most important Fanconi anemia gene to be discovered to date," said Lynn Frohnmayer. "At our recent meeting of over 150 researchers in Amsterdam, scientists praised the cloning of this new gene and related discoveries about the protein pathway as the most significant advances of the year. We are hopeful that this greater understanding of Fanconi anemia will lead to vastly improved therapies and a cure."

Fanconi Anemia Facts

  • FA causes bone marrow failure. Bone marrow slowly stops making red and white blood cells, and platelets.
  • It is a recessive disorder, which means when both parents carry a defect in the same FA gene, there is a 25 percent chance that their child will be born with the disease.
  • Many FA patients develop acute myelogenous leukemia. Older patients may develop other cancers.
  • Many patients do not reach adulthood.
  • The disease usually reveals itself between the ages of 3 and 12.
  • Sometimes the disease is evident at birth through birth defects, such as thumb and arm defects.

Editors note: Readers interested in supporting the Fanconi Anemia Research Fund can mail their donations to 1801 Willamette St., Suite 200, Eugene, Oregon, 97401 or call 541 687-4658 for more information.