Mutation Scars Hearts

Scientists have found a mutation that leads to an inherited form of heart failure. The defective gene, reported in the 1 May issue of Science, may help researchers understand what makes the heart tissue slowly waste away--and how to slow this disease's progression.

Although the most common cause of heart failure is arterial clogging, more than 100,000 people a year die from a gradual deterioration of the heart muscle, a condition called dilated cardiomyopathy. For some reason, heart muscle cells die, turn to scar tissue, and prevent the heart from pumping blood effectively. Because previous studies had indicated that up to 50% of cardiomyopathy cases are inherited, Timothy Olson, Mark Keating, and their colleagues at the University of Utah and Minnesota's Mayo Clinic decided to survey families with the disease for defects in a likely gene.

They focused on the gene for actin, a protein that links contracting muscle cells, because studies in mice and flies have indicated that minor defects in actin genes can disable a muscle. The group compared the actin gene sequences of people in two families in which the disease had been diagnosed in more than one member. Of 12 people tested, eight had one of two defective nucleotides in their actin gene. All eight had the disease or an enlarged heart, an early symptom. Olson says it's not yet clear what these mutations may be doing to the actin molecule.

"This is an important paper," says Michael Bristow, a cardiologist at the University of Colorado Health Sciences Center in Denver. If researchers can identify people with faulty actin genes, they may be able to treat the disease more effectively. "Earlier treatment with beta-blockers, which decrease the mechanical stress on the heart, may attenuate the progression of the disease," Olson says.