An international team of researchers has made a critical advance in determining the cause of a common form of muscular dystrophy known as facioscapulohumeral dystrophy (FSHD).
They have identified a DNA sequence in individuals with FSHD that causes a gene called DUX4 to be more active. Previous work from this research team and others has shown that this gene produces a protein that is toxic to muscle cells, and the current study indicates that it is likely to be key to developing FSHD. This finding points to potential new drug targets for treating – or potentially curing – FSHD.
The findings, published in Science, shed new light on how a genetic mutation identified nearly 20 years ago causes the disease. The mutation is associated with the majority of FSHD cases, which affects some 300,000 people worldwide, according to a press release.
Silvere van der Maarel, PhD, professor of medical epigenetics in the Department of Human Genetics at Leiden University Medical Center in the Netherlands, led the study in collaboration with researchers at the University of Leiden in the Netherlands. His co-authors include: Fred Hutchinson at the Cancer Research Center; Stephen Tapscott, MD, PhD, at the Hutchinson Center; Dan Miller, MD, PhD, at the University of Washington; and Rabi Tawil, MD, at the University of Rochester Medical Center.
“In contrast to most genetic diseases, knowledge of the genetic mutation did not explain the cause of the disease,” Tapscott, a member of the Human Biology Division at the Hutchinson Center and an expert in neurogenetics and neuromuscular disease, stated in a the release. “Although many different models and hypotheses were proposed for how the FSHD mutation might cause the disease, none had sufficient experimental support to attain legitimacy, which resulted in controversy and slow progress in FSHD research. These new findings provide a single, testable hypothesis.”