A second critical advance has been made by scientists in determining the cause of a common form of muscular dystrophy known as facioscapulohumeral dystrophy, or FSHD.
In August 2010, an international team of researchers led by an investigator from Fred Hutchinson Cancer Research Center published a landmark study that established a new and unifying model for the cause of FSHD.
Their current work shows that the disease is caused by the inefficient suppression of a gene that is normally expressed only in early development. The work will lead to new approaches for therapy and new insights into human evolution.
The disease-causing gene, called DUX4, 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."
In contrast, 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," said corresponding author Stephen Tapscott, a member of the Hutchinson Center's Human Biology Division.
"The occasional 'bursts' of DUX4 are thought to be toxic to the muscle cells, which leads to muscle cell death and the muscular dystrophy."
The study has been published in PLoS Genetics.