September 4, 1998 

Robert Brown Jr., MD

Gene causes two types of MD

An international research team based at the MGH has discovered a gene that, when mutated, causes two types of muscular dystrophy. The gene, found on chromosome 2, codes for a novel protein called dysferlin, produced in skeletal muscles. Mutations in dysferlin were seen in several families in which members had either Miyoshi myopathy, a very rare muscle disorder, or one form of limb girdle muscular dystrophy, a more common condition. The report appears in the September issue of Nature Genetics.

"It's an interesting twist that this gene is associated with two forms of muscular dystrophy," says Robert Brown Jr., MD, director of the Day Neuromuscular Research Laboratory at the MGH and leader of the study. "We started working on what we thought was a very rare, orphan disease and found that our work also applied to a more abundant form. It appears that 5 to 10 percent of cases of muscular dystrophy may result from mutations in this gene." He adds that identifying the gene will help improve diagnosis of these particular disorders and eventually could lead to treatment methods that address specific muscle defects.

The current discovery caps a process that began 15 years ago when Brown met with members of a family affected by an unusual muscle disorder the researchers named "Miyoshi myopathy," after the Japanese professor who originally described a similar condition.

Because the disorder was so rare, Brown's team worked with collaborators from around the world to search for other families with the same problem. Eventually the project included researchers from Spain, France, Italy, Tunisia, Saudi Arabia, Canada and Japan, as well as from other US institutions. The first author on the current paper is Jing Liu, PhD, formerly of Brown's lab and now with the Phage Tech Company of Montreal.