Occasionally, you hear of a young adult who seemed healthy but suddenly dropped dead of a heart attack. Sometimes the person has inherited a disorder called long QT syndrome in which the heart takes too much time to relax after a contraction and develops a dangerous irregular rhythm. researchers have now shown how certain genetic defects in these patients cause heart cells to work properly. The results could help doctors decide whether someone with long QT syndrome need treatment or can simply be watched.
Doctors often detect long QT syndrome with a routine electrocardiogram. But patients with only moderately abnormal pattern of long QT does not always develop severe clinical symptoms, and doctors have no easy way to predict who is at risk and should receive treatment. "Physicians want to know the risk of drop dead tomorrow. It's really the quagmire in this area," says George Alfred human geneticist from Vanderbilt University in Nashville.
Another source of information is genetics. long QT syndrome is caused by defects in ion channels, proteins that keep heart beat by controlling the flow of ions across the membrane of heart cells. doctors may order a test to find out that the mutation a patient, but until now they did not know what the change meant for risk.
biophysicist Coeli Lopes and colleagues at the University of Rochester Medical Center in New York wanted to know that these mutations actually do. They focused on a gene linked to more than 50% of cases of long QT syndrome, which encodes a protein named KCNQ1, which is part of a potassium channel. Working with collaborators Japan, Denmark and the Netherlands, they collected medical records for 387 patients from families with long QT syndrome who carried a copy of 17 common mutations in the KCNQ1 gene.
The researchers engineered frog eggs to express the 17 abnormal forms of KCNQ1 and measure how cells transmitted electric currents. Some mutations have the potassium channels carry less current channels and open more slowly than normal. When the group of Lopes checked the medical history of patients, the researchers found that those with slowly activating channels were twice as likely as patients with other mutations to die before age 30 or develop severe symptoms such as fainting or heart attacks.
"We could link the specific dysfunction to heart risks," said Lopes. Clinicians could use this information and the factors they already use, such as age and sex to determine if a patient has need treatment, such as beta-blockers medications or an implanted defibrillator, she said. the study appears today in Science Translational medicine .
"They did something interesting here "by showing that a measure specimen corresponds with what happened to patients, said George, who was not involved in the work. He noted, however, that the double risk should be confirmed in other studies before they can be used in the clinic. "You can not write the final rules yet."
cardiologist and geneticist Calum MacRae from Massachusetts General Hospital in Boston is also cautious. He stresses that often two different families carry the same mutation, but one family develops symptoms, suggesting that other genetic factors also affect the risk. However, "this is a good first step in understanding what these mutations do," he said.
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