An International Collaboration Identifies a Region of DNA

An international collaboration identifies a region of DNA necessary for FSHD and focuses attention on DUX4 as the cause of muscle deterioration

            An international research collaboration that includes research groups funded by the Friends of FSH Research has made a critical advance in determining the cause of facioscapulohumeral dystrophy (FSHD).  The mutation that causes the majority of FSHD cases was identified almost two decades ago but, in contrast to most genetic diseases, knowledge of the genetic mutation did not explain the cause of the disease.  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. The recent publication in Science magazine focuses research on a single and testable hypothesis. Their work identified a DNA variation (polymorphism) necessary for FSHD that occurs outside the mutation region and is necessary for FSHD.  This DNA sequence in individuals susceptible to FSHD acts to stabilize the product of the DUX4 gene, whereas individuals not susceptible to FSHD have a different DNA sequence that does not stabilize DUX4.  This finding provides a new and unifying model for FSHD because it focuses studies on determining whether the DUX4 protein causes FSHD, as indicated by this group’s genetic analysis. 

            This study, published in Science magazine, was led by Dr. Silvere van der Maarel at the Leiden University Medical Center, together with Dr. Rabi Tawil at the University of Rochester, Dr. Stephen Tapscott at the Fred Hutchinson Cancer Research Center in Seattle, and Dr. Dan Miller at the University of Washington in Seattle. Rapid progress was made possible by an unusual degree of collaboration and data-sharing among the individual groups at yearly workshops sponsored by the Friends of FSH research.  The Friends of FSH Research, as well as the Shaw Family Foundation, sponsored yearly workshops that brought these collaborators together to share their research and also funded research in the laboratories of two of the groups (Dr. Stephen Tapscott at the Fred Hutchinson Research Center and Dr. Daniel Miller at the University of Washington). The initial progress supported by the Friends of FSH Research resulted in successful grant applications to the National Institutes of Health to continue their FSHD research studies.