Muscular Dystrophy Gene Riddle Cracked, May Lead to Treatments

A genetic flaw behind a common form of muscular dystrophy may be explained in research that suggests why some people with the variant gene are afflicted with the muscle-wasting disease.

While scientists have known for more than a decade that facioscapulohumeral muscular dystrophy, or FSHD, is linked to genetic abnormalities on the end of chromosome 4, not everyone with these changes gets the disease, said Daniel Miller, a genetics researcher at the University of Washington in Seattle. The findings show that strings of genetic code surrounding a critical gene can either disable it or allow it to be expressed and damage cells, Miller said.

The results may help scientists develop new drugs to treat the condition, which generally strikes children and causes weakness that begins in their facial muscles and shoulders, then spreads down the body, Miller said. About 1 in 20,000 people worldwide have FSHD, according to the report published today in the journal Science.

“Prior to this, if you wanted to develop a drug, you didn’t know exactly which genes caused it,” Miller said. “This allows us to focus drug development on a specific biological target.”

Miller was part of an international team of researchers in the Netherlands, France and Spain hunting for the cause by scanning the genes of patients and analyzing small differences in the sequences surrounding a critical gene.

No Longer ‘Junk’

That gene, called DUX4, is part of a long stretch of repeating genetic code that researchers had long considered unimportant or “junk” DNA, Miller said. The research team, led by Silvere M. van der Maarel at Leiden University Medical Center in Leiden, Netherlands, narrowed the region of importance to a few letters of genetic code.

“You can have two people with similar mutations and one will get disease, the other will not,” said Miller, an associate professor of pediatrics and co-author of today’s report. “This finding connects pieces of a puzzle that were previously considered unrelated.”

The team discovered changes in the number of repeated letters that either silenced DUX4 or allowed it to be expressed, Miller said.

“These changes allow DUX 4 to be made when it normally would be degraded,” Miller said. “We think DUX 4 is poisonous to most cells and may be what’s killing muscle cells.”

The study was funded by the Netherlands Organization for Scientific Research, the U.S. National Institutes of Health and other organizations.