Discovery of the Marfan syndrome gene, whose existence was predicted 35 years ago by Dr. Victor A. McKusick, a Johns Hopkins cardiologist, is reported in today's issue of Nature, a British journal.
Scientists from Johns Hopkins and the Portland (Ore.) Shriners Hospital have proved that the gene responsible for making a connective tissue protein causes the syndrome, a potentially fatal, inherited disorder affecting one in 10,000 Americans, the journal reports.
The tall and long-armed Abraham Lincoln is believed to have had it. Olympic volleyball player Flo Hyman and University of Maryland basketball player Chris Patton died of it when their aortas -- the heart's major blood vessel -- burst despite apparently excellent health.
The finding is expected to have immediate use in early diagnosis of patients before symptoms appear and in prenatal diagnosis where the gene, which is altered in Marfan patients, can be tracked through families, says Dr. Harry C. Dietz, lead author of the Hopkins-Shriners Hospital paper, one of three related articles in Nature.
The gene is on chromosome 15 and normally makes the protein fibrillin, a component of connective tissue, the scaffolding that holds together skin, muscles and organs.
The mutated gene in Marfan's patients either makes too little of this scaffolding or makes weak or broken scaffolding. Since connective tissues exist everywhere in the body, a defective gene can affect a number of organs, but most commonly the heart, eyes, bones and skin.
The Hopkins-Shriners Hospital report shows that a particular alteration in the gene was present in patients with Marfan's and not in people without the syndrome.
"That was the final proof that the fibrillin gene was the gene responsible for Marfan syndrome," Dietz says.
The clustering of abnormalities that McKusick, a pioneer and world authority on Marfan syndrome and other connective tissue diseases, saw in some of his heart patients in the 1950s at Hopkins led him to determine that a single genetic defect in connective tissue must be behind the long arms and long legs, dangerous weakening of the aorta and dislocated eye lenses -- all characteristic of Marfan's.
The stretched, fragile aorta can rupture and cause sudden death and the dislocated eye lenses can lead to blindness.
Evidence suggests that the earlier a patient is diagnosed and started on medication, the better his or her chances of long-term, quality survival, says Dietz, a research geneticist.
