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The gene for the most common adult form of muscular dystrophy has been isolated by an international team of geneticists, including several at MIT, whose work was published in the Feb. 21 issue of the journal Cell.
The Muscular Dystrophy Association (MDA), which funded much of the work, said the finding is a major step closer to early detection and the eventual treatment of myotonic dystrophy, which affects one in 7,000 to 8,000 people worldwide.
Dr. J. David Brook of the Center for Cancer Research was the principal researcher in the United States and the lead author of the Cell paper. He is a postdoctoral fellow in the laboratory of Professor David E. Housman, also one of the paper's authors. The disclosure followed by two weeks the announcement by Dr. Housman and other researchers in the international group that they had linked a specific genetic defect to muscular dystrophy and made the surprising discovery that the genetic flaw can worsen with each generation.
Three teams of scientists cooperated in the work reported in Cell and detailed at a news conference held February 20 in Rm E25-117. Joining Dr. Brook there were Dr. Duncan J. Shaw, who led a group at the University of Wales College of Medicine in Cardiff, and Dr. Keith Johnson, who headed a group at the Department of Anatomy at Charing Cross and Westminster Medical School. Professor Housman, who was out of the country, could not attend the news conference.
Other MIT authors, many of whom also attended, are Mila E. McCurrach, Alan J. Buckler, Deanna Church, Hiroyuki Aburatani, Kent Hunter, Vincent P. Stanton, Jean-Paul Thirlon, Thomas Hudson, Robert Sohn and Boris Zemeiman, all of the Center for Cancer Research and Professor Housman's laboratory.
Also attending were several representatives of the Boston office of the MDA and, at their invitation, three people who are affected by myotonic dystrophy. The association arranged for the news conference to be videotaped and later broadcast it by satellite to the 200 TV stations that carry the Jerry Lewis telethon on Labor Day weekend that raises money for muscular dystrophy research and treatment.
Professor Richard O. Hynes, director of the Center for Cancer Research, praised the work of the international team and the Muscular Dystrophy Administration for its financial support and for strongly fostering the spirit of cooperation that brought the important findings more quickly to hand.
Dr. Richard T. Moxley III of the University of Rochester, a neurologist and pediatrician who has studied and treated the disease for 18 years, also spoke at the invitation of the MDA. He gave a medical doctor's view of the importance of the findings and how they are likely to affect detection, treatment and followup. Dr. Moxley, who said he has close relatives who suffer from myotonic dystrophy, also praised the MDA practice of encouraging various teams of scientists to work cooperatively.
In explaining their work at the news conference, Dr. Brook, Dr. Johnson and Dr. Shaw told the story chronologically, going back to the mid 1980s. They described the hunt for the specific gene in terms of an encyclopedia of 26 volumes. The entire set represents the human genome. The work published three weeks ago, which reported the identification of the area on the genome where the defect was likely to occur, was compared to identifying one of the 26 volumes. Locating the specific gene was compared to finding the specific page in the volume that contained a defective word, then locating the word.
The researchers reported that by using positional cloning strategies they had identified a chemical sequence within a gene at the end of one of the long arms of chromosome 19. The sequence is a CTG triplet, meaning that those segments of DNA which scientists identify by the letters C, T and G are found to repeat in that order. The repeat occurs between 5 to 27 times in those unaffected by myotonic dystrophy. But in those with the disease, the repeat is found to be copied from 50 to several thousand times. The larger the number of repeats, the more severe the effects of the disease, the researchers reported.
The number of repeated sequences can change in succeeding generations and children born to parents who are only minimally affected can show very severe symptoms.
Dr. Brook said the myotonic dystrophy gene is linked to the production of a protein that plays an important role in many different tissues in the body and an abnormality involving it could affect several organs.
"Unraveling the connections between expansion of the CTG repeats and the symptoms of myotonic dystrophy is an important challenge for future investigators," Dr. Brook said. "The fact that this gene appears to direct the production of this type of protein opens a broad range of physiological questions that should be directly tested," Dr. Shaw said.
It was also announced at the press conference that two papers to be published in Science on March 6 will confirm the work reported at MIT on February 20. The MDA, which made that announcement, said that Science had lifted its usual embargo on premature disclosure of scientific work it will publish.
Myotonic dystrophy leads to weakness and wasting of voluntary muscles and often produces myotonia, or difficulty in relaxing muscles. The disorder can also have a wide variety of other effects, including gastrointestinal complications, cataracts, heart problems, premature balding, mental slowness and sleep disorders.
The condition, also known as myotonica and Steinert's disease, usually appears in adolescence or early adulthood. An often fatal form is present at birth. In adults, death may result in the 50s or 60s from heart or respiratory failure.
A version of this article appeared in the February 26, 1992 issue of MIT Tech Talk (Volume 36, Number 21).