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University of Pittsburgh cardiologists identify new cardiac arrest gene
Date:10/31/2007

lator into the chests of patients who are clinically found to be at high risk.

In this study we found that GPD1-L, while not an ion channel itself, is a trafficking gene that allows the sodium channel to find its way to the cell membrane. The mutation interferes with the trafficking and leads to potentially fatal arrhythmias, said Dr. London. Equally important, we suspect that the function of the native GPD1-L gene and the mutant are influenced by oxidative stress, a process which interferes with the bodys natural ability to repair itself from antioxidant assaults, e.g., pollution, smoking or stress. Also, patients with Brugada syndrome only rarely have symptoms; they have this genetic mutation all the time. So, the question now is, why do arrhythmias or sudden death happen on any one particular day" Something else is happening concurrently with this mutation to trigger the potentially lethal rhythm problems. With the identification of this new GPD1-L gene, we hope to identify other new genes along with entirely new pathways that stabilizes the rhythm of the heart, increasing our understanding of the mechanisms that lead to sudden death in this particular condition, added Dr. London.

Using positional cloning and gene sequencing on a family affected with Brugada syndrome, Dr. London and colleagues identified a mutation in a previously unstudied gene, GPD1-L, on chromosome 3p24. This mutation impairs the hearts natural electrical ability to beat in a coordinated manner and maintain a stable rhythm. To date, only ion channel genes had been shown to cause Brugada syndrome.

The patient affected with Brugada syndrome in this study was first referred to Dr. London and colleagues more than 10 years ago. Since that time, a total of 195 family members have now been enrolled and ECGs have been repeated every six months. To date, implantable cardiac defibrillators (ICDs) have been placed in four affected patients. The original family member has had
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Contact: Maureen McGaffin
McGaffinME@upmc.edu
412-647-3555
University of Pittsburgh Schools of the Health Sciences
Source:Eurekalert

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