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Gene's newly explained effect on height may change tumor disorder treatment
Date:8/11/2008

St. Louis, August 11, 2008 A mutation that causes a childhood tumor syndrome also impairs growth hormone secretion, researchers at Washington University School of Medicine in St. Louis have found.

The discovery provides new insights into an old mystery, revealing why patients with neurofibromatosis type 1 are frequently shorter than their peers. The surprising details have led scientists to consider modifying their search for treatments for the inherited disorder, which is caused by a mutation in the neurofibromin 1 (NF1) gene and is characterized by an increased risk of cancer.

"We've learned that the NF1 gene affects stature through a different pathway than the one we've previously focused on to understand cancers in patients with neurofibromatosis type 1," says Washington University neurologist David H. Gutmann, M.D., Ph.D., a Washington University neurologist who treats individuals with neurofibromatosis at St. Louis Children's Hospital. "Given that this second pathway has been linked to cancer in other contexts, we may need to consider the possibility that it is contributing to these tumors and alter our treatment goals accordingly."

The results appear online in the journal Human Molecular Genetics.

Neurofibromatosis 1 affects more than 100,000 people in the United States and is one of the most common tumor predisposition syndromes. The severity of the condition varies.

The NF1 protein, called neurofibromin, influences a number of different growth control pathways. Until now, much research focused on neurofibromin's effects on RAS protein activity, which is linked to cell growth, proliferation and cancer. Normally, NF1 deactivates RAS proteins. In its absence, scientists believe unchecked RAS can promote cancer development.

To learn more, Gutmann's lab created a line of mice in which stem cells in the brain do not make the NF1 protein. They found that these mice were significantly smaller t
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Contact: Michael C. Purdy
purdym@wustl.edu
314-286-0122
Washington University School of Medicine
Source:Eurekalert

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