Muscular dystrophies or MD are a group of more than 30 genetic diseases characterized by progressive weakness and degeneration of the skeletal muscles that control movement. New research is now helping establish a new and unifying model for the cause of a common type of MD called facioscapulohumeral dystrophy.



Facioscapulohumeral refers to the muscles that move the face, shoulder blade, and upper arm bone. This form of muscular dystrophy appears in the teens to early adulthood. Investigators from Fred Hutchinson Cancer Research Center found the disease is caused by the inefficient supression of a gene that is normally expressed only in early development.



Called DUX4, this disease-causing gene previously had been thought to be a completely inactive gene in humans. DUX4 belongs to a special class of genes called retrogenes, which usually represent unused byproducts of evolution that have no remaining biological function, sometimes called "dead genes."



The researchers discovered that the DUX4 protein is abundantly expressed in human germ-line cells, the cells that form the sperm and eggs, which indicates a necessary function early in development. Normally, the DUX4 gene is suppressed in all other cells of the body. However, the mutation that causes FSHD makes this suppression less efficient.



"The result is that the DUX4 gene occasionally escapes the inefficient suppression and is expressed in some muscle cells, similar to the Old Faithfull geyser that is usually off but occasionally releases a burst of water," Stephen Tapscott, M.D., Ph.D., a corresponding author and a member of the Hutchinson Center's Human Biology Division was quoted saying. "The occasional 'bursts' of DUX4 are thought to be toxic to the muscle cells, which leads to muscle cell death and the muscular dystrophy."



They also say the study will lead to new approaches for therapy and new insights into human evolution.



SOURCE: PloS Genetics, November 2010