More than a decade ago, researchers at the University of Pittsburgh began studying a northwestern Pennsylvania family with Brugada syndrome, a rare, inherited heart rhythm disorder that can cause sudden cardiac arrest. That effort, along with those of other investigators, has led to identification of a gene whose mutation can cause the arrhythmia. Those research findings, published in the journal Circulation.
Brugada syndrome, which can be detected on an electrocardiogram, can cause fainting or sudden death. There is no cure, and the best therapy to date involves implanting a defibrillator into the chests of patients at high risk. In about 20 percent of Brugada syndrome cases, mutations in the heart’s sodium channels lead to less current flow and shorter heartbeats in part of the heart. The sodium channels are involved in changing the electrical properties of heart muscle cells, and are necessary to start the impulses associated with each heartbeat.
By contrast, cases caused by mutation of the gene identified by the Pitt-led study are comparatively rare, said Dr. Barry London, chief of cardiology at the Pitt School of Medicine and lead author of the study. In those cases, the mutation appears to interfere with the sodium channel’s ability to find its way to the cell membrane, leading to potentially fatal arrhythmias, Dr. London said.
Researchers suspect that the function of the normal gene and its mutation are influenced by stress, which can be affected by such factors as fever, pollution or smoking. However, Dr. London noted that more study is needed to determine how the gene works and interacts with other genes.
The gene, known as GPD1-L, on chromosome 3p24, is the second whose mutation is known to cause Brugada syndrome, he said. The first was identified nearly a decade ago by other researchers, and a third and fourth have recently been identified, he said.
Dr. London noted that some study collaborators have shown that mutations in GPD1-L also cause other heart rhythm problems. In a related study in the same journal issue, Dr. Michael Ackerman, director of the Mayo Clinic Windland Smith Rice Sudden Death Genomics Laboratory, and his colleagues screened GPD1-L in infants who died of sudden infant death syndrome and found three mutations.
Perhaps 1 percent of SIDS cases are linked to such mutations, Dr. London said, and up to one-third of cases are related to inherited heart rhythm defects. The family study began more than a decade ago when a man who had fainted at work was referred to Pitt researchers. Since then, they have studied 195 family members, many in Pennsylvania but some as far away as California.
The genetic defect was found in more than 30 family members, Dr. London said. Some had fainting spells and electrocardiogram changes, while others did not show abnormal heart rhythms. Four have had defibrillators implanted that can shock the heart back to a normal rhythm if it stops beating.
Dr. London said the first family member treated in the study had two of those episodes soon after the defibrillator was implanted, but has since had no others. The other three family members have not had problems requiring the device to activate, he said.
Besides Drs. London and Ackerman, other study collaborators include Michael Michalec, Dr. Haider Mehdi, Dr. Xiaodong Zhu, Laurie Kerchner, Dr. Prakash C. Viswanathan, Dr. Mohan Madhusudanan, Dr. Catherine Baty, Stephen Lagana, Dr. Ryan Aleong, Rebecca Gutmann and Dr. Dennis McNamara, all of the University of Pittsburgh; Dr. Raul Weiss of Ohio State University; and Drs. Samuel C. Dudley Jr., Arnold E. Pfahnl, Shamarendra Sanyal and Lijuan L. Shang, all of Emory University and the Atlanta VA Medical Center. Post-Gazette NOW.