Clue to Adult Muscular Dystrophy

RNA segments may be "piling up" in cell centers, causing muscle weakness in adults with a common form of muscular dystrophy.

This cellular traffic jam is the latest finding by pathologists at Baylor College of Medicine who are seeking new information about why patients with myotonic dystrophy often experience muscle weakness because their cells are not taking in enough blood sugar. Myotonic dystrophy, which results in progressive degeneration of the head, neck and arm muscles, can also cause cataracts, endocrine problems and mental retardation. The disorder occurs in one in 8,500 people and tends to run in families.

"An early symptom for myotonic dystrophy is an unusual form of insulin resistance due to a defect in skeletal muscle," said Dr. Thomas A. Cooper, associate professor of pathology. "Insulin receptors are important for normal metabolism of glucose. You eat a meal, your blood sugar goes up and your pancreas stimulates insulin. The insulin binds to a receptor in the muscle to stimulate glucose uptake from the blood. The problem with myotonic dystrophy patients is that the insulin receptor in muscle is abnormal."

Dr. Cooper said these patients' glucose levels are too high after a meal because they simply do not take enough glucose into the muscle.

Dr. Cooper and Drs. Rajesh S. Savkur and Anne V. Philips found that in myotonic dystrophy patients, a basic process of gene expression is abnormal. The mutated gene causing myotonic dystrophy was identified in 1992. How the mutation causes the disease is still a mystery.

"The mutation is a copying error of the gene resulting in hundreds of thousands of copies of a small region of the gene. When the gene is turned on, this repeat clogs up the nucleus and wreaks havoc with the body's ability to regulate other genes, such as the insulin receptor," Dr. Cooper said. "The result is that the wrong form of the insulin receptor is in muscle, greatly slowing down the muscle's intake of blood glucose."

"In healthy individuals, there are rarely more than 35 RNA repeats," Dr. Cooper said. "We believe the high number of repeats and accumulated RNAs seen in myotonic dystrophy patients is causing an aberrant regulation of splicing in the insulin receptors. This is exciting because it is a new way for a mutation to cause human disease."

The team's findings are published in the September issue of Nature Genetics.

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©2006 Texas Medical Center

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