Singapore, Aug 20, 2010: Nearly two decades after identifying the specific genetic flaw that causes a common type of muscular dystrophy, scientists believe they have figured out how that flaw brings about the disease. The finding by an international team of researchers settles a longstanding question about the roots of facioscapulohumeral muscular dystrophy or FSHD. The work is published in the August 20, 2010 issue of Science.

Unraveling how the genetic defect causes FSHD has been especially challenging for scientists. Unlike with many genetic diseases, their identification of the mutation that is the basis of FSHD did not quickly lead to a deeper understanding of how the disease actually comes about. The lack of clarity has posed a significant barrier to researchers hoping to turn the knowledge of the genetic flaw into significant progress for patients.

The latest findings clarify the picture significantly. Scientists have discovered that several deleted versions of a gene trigger the remaining copies of that gene to be much more active than usual. That's because the DNA that codes for the gene is not as tightly coiled or elusive to the body's molecular machinery as usual when some copies are missing, and so the gene – known as DUX4, which makes a protein harmful to muscle cells – is more active than it should be.

The work offers up a new therapeutic target to scientists aiming to develop a treatment or cure for the disease.

The research was led by genetics researchers at the University of Leiden in the Netherlands, working together with scientists at the University of Rochester Medical Center, the Fred Hutchinson Cancer Research Center in Seattle, and other investigators.