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Closing in on Lethal Heart Rhythm in Young Athletes

each year from ARVD.

'We expect a test for DSG2 mutations to be available to those with a family history of the condition before the end of the year,' he says. The same Hopkins team developed a blood test to screen for PKP2 mutations. That test became available in May and is currently the only one available for detecting those at greater risk of the disease.

More than 400 people have been screened at Hopkins so far and of these, two-thirds have had serious enough forms of the condition to warrant implantation of a defibrillator, an electrical device that corrects any disturbances in the heart's rhythm.

The Hopkins researchers identified the DSG2 mutation through genetic analysis of blood taken from 60 men and women already diagnosed with ARVD. All were part of a patient database created at Hopkins in 1998. The researchers focused on cell-adhesion proteins because they had already been linked to Naxos syndrome, which produced symptoms in the right ventricle similar to those documented in ARVD.

When scientists excluded their ARVD patients with PKP2 mutations, they were left with 33 who had no known genetic explanation for their condition. Additional testing revealed the four mutations in DSG2.

'We knew right away that we had found something very significant,' says lead author Mark Awad, B.A., a medical and predoctoral sciences student at Hopkins. 'The mutations were confined to a highly functional part of the gene and were highly conserved, meaning that evolution had not drastically changed the genetic sequence over time - the gene was kept the way it was because it was important to the heart’s normal function.'

According to Awad, not everyone with a genetic mutation develops ARVD. He adds that further analysis of the condition’s genetic roots will help researchers to calculate the precise increased risk from each mutation for developing symptoms and dying. Previous research by the Hopkins team sh
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