Scientists make second critical advance in muscular dystrophy research

Scientists have made a second critical advance 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 at the Fred Hutchinson Cancer Research Centre in the US 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 inefficient suppression of a gene that is normally expressed only in early development. The work will lead to new approaches for therapy, and offer 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 by-products 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 that the gene has a necessary function early in development.

Normally, the DUX4 gene is suppressed in all other cells of the body. But 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," said corresponding author Stephen Tapscott, a member of the human biology division at the centre.

"The occasional 'bursts' of DUX4 are thought to be toxic to the muscle cells, which leads to muscle cell death and muscular dystrophy."

The study has been published in PLoS Genetics.