Ataxia-Telangiectasia

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What is ataxia-telangiectasia?

Ataxia-telangiectasia is a rare inherited disorder of childhood that affects the nervous system, immune system, and other body systems.

This disorder is characterized by progressive difficulty with coordinating movements (ataxia) beginning in early childhood. Affected children typically develop difficulty walking, problems with balance, abnormal eye movements, and slurred speech. Small clusters of enlarged blood vessels called telangiectases, which occur in the eyes and on the surface of the skin, are also characteristic of this condition.

People with ataxia-telangiectasia often have weakened immune systems, and many develop chronic lung infections. They are also at an increased risk of developing cancer, particularly cancer of blood-forming tissue (leukemia) and cancer of immune system cells (lymphoma). Affected individuals are very sensitive to the effects of radiation exposure, including medical x-rays. Although people with ataxia-telangiectasia usually live into adulthood, their life expectancy is reduced.

How common is ataxia-telangiectasia?

This condition occurs in 1 in 40,000 to 100,000 people worldwide.

What genes are related to ataxia-telangiectasia?

Mutations in the ATM gene cause ataxia-telangiectasia.

The ATM gene provides instructions for making a protein that helps control cell division and is involved in DNA repair. This protein plays an important role in the normal development and activity of several body systems, including the nervous system and immune system. Mutations in the ATM gene reduce or eliminate the function of the ATM protein. Without this protein, cells in the brain die inappropriately, particularly in a part of the brain involved in coordinating movements (the cerebellum). The loss of these brain cells causes the movement problems characteristic of this disorder. Mutations in the ATM gene also prevent cells from responding correctly to DNA damage, which allows genetic defects to accumulate and can lead to cancer.

How do people inherit ataxia-telangiectasia?

Ataxia-telangiectasia is inherited in an autosomal recessive pattern, which means two copies of the ATM gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.

About 1 percent of the United States population (2.5 million people) carry one mutated copy and one normal copy of the ATM gene. Although they do not have ataxia-telangiectasia, they are more likely than people without an ATM mutation to develop cancer, particularly breast cancer. Carriers of a mutation in the ATM gene also may have an increased risk of heart disease.

Source: National Institutes of Health

Reports from University of North Carolina, Center for Environmental Health and Susceptibility advance knowledge in ataxia telangiectasia therapy

"Profiles of global gene expression in AT cells were determined at 2, 6, and 24 h after treatment with 1.5-Gy IR or sham treatment and were compared with those previously recognized in normal human fibroblasts. Under basal conditions, 160 genes or expressed sequence tags were differentially expressed in AT and normal fibroblasts, and these were associated by gene ontology with insulin-like growth factor binding and regulation of cell growth. On DNA damage, 1,091 gene mRNAs were changed in at least two of the three AT cell lines. When compared with the 1,811 genes changed in normal human fibroblasts after the same treatment, 715 were found in both AT and normal fibroblasts, including most genes categorized by gene ontology into cell cycle, cell growth, and DNA damage response pathways. However, the IR-induced changes in these 715 genes in AT cells usually were delayed or attenuated in comparison with normal cells," wrote T. Zhou and colleagues, University of North Carolina, Center for Environmental Health and Susceptibility.

The researchers concluded: "The reduced change in DNA damage response genes and the attenuated repression of cell cycle-regulated genes may account for the defects in cell cycle checkpoint function in AT cells."

Zhou and colleagues published their study in Molecular Cancer Research (Ataxia telangiectasia-mutated dependent DNA damage checkpoint functions regulate gene expression in human fibroblasts. Molecular Cancer Research, 2007;5(8):813-22).

For more information, contact T. Zhou, University of North Carolina at Chapel Hill, Dept. of Pathology and Laboratory Medicine, Center for Environmental Health and Susceptibility, CB#7295, Chapel Hill, NC 27599-7295 USA..

Publisher contact information for the journal Molecular Cancer Research is: American Association Cancer Research, 615 Chestnut St., 17TH Floor, Philadelphia, PA 19106-4404, USA.

Keywords: United States, Chapel Hill, Ataxia Telangiectasia Therapy, Ataxia-telangiectasia, Cancer, Cancer Research, DNA Damage, DNA Research, Deoxyribonucleic Acid, Dermatology, Environmental Health, Genetics, Neurology, Oncology, Proteomics, Telangiectasia.

This article was prepared by Clinical Oncology Week editors from staff and other reports. Copyright 2007, Clinical Oncology Week via NewsRx.com.