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Last Updated: Nov 18, 2006 - 12:32:53 PM

Cardiology Channel
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Latest Research : Cardiology

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Genetic clues to cardiomyopathy's origins
Aug 19, 2006 - 5:44:00 PM, Reviewed by: Dr. Sanjukta Acharya

"We now have the genetic ability � that is, making a diagnosis off of a blood test of the gene � to evaluate these patients from the perspective of the disease's origin"

 
A genetic discovery sheds new light on the cause of cardiomyopathy and sudden death in young adults, which originates in the previously overlooked right ventricle of the heart, said a researcher at Baylor College of Medicine (BCM) and Texas Children's Hospital (TCH) in Houston.

In a report that appears online today in the journal Circulation Research, Dr. Jeffrey Towbin, professor of pediatrics at BCM and chief of pediatric cardiology at TCH, reports that a study in mice identifies conclusively for the first time genetic origins of cardiomyopathy, one of the leading causes of sudden cardiac death in young adults.

"We are getting to the underlying cause of this disease," said Towbin, principal investigator of the study. "For the first time, we have taken a human disease gene and put it into an animal model so that we can study its mechanisms in greater detail."

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is a rare, progressive condition that causes diseased heart muscle and impairs cardiac function. In many cases, ARVC leads to fatigue, irregular heartbeat (arrhythmia), and, potentially, heart failure and sudden cardiac death.

In a previous study, Towbin and colleagues first identified mutations in the desmoplakin gene, which encodes a protein in the connecting junction between heart cells. In this study, funded by the National Institutes of Health and the National Heart, Lung, and Blood Institute, the authors implanted a mutant human desmoplakin gene into mice, which resulted in the mice's cardiac integrity being compromised, leading to dilation of the right ventricle, buildup of scar and fatty tissue, and arrhythmia.

Towbin calls ARVC "underrecognized" in the United States primarily because of its relative newness and difficulty evaluating the right ventricle technically, which can lead to misdiagnosis and improper treatment. Statistics of its prevalence in the United States have yet to be determined, but in Italy the disease is known to be the leading cause of sudden cardiac death in otherwise healthy young adults.

"ARVC is underrecognized here in the United States because of the novelty of the disorder and the lack of advances in technology that assess the right ventricle," said Towbin. "But I predict that in the next several years this will be shown to be a key player in sudden cardiac death."

The new findings will help pediatric and adult cardiology experts better understand the root cause of ARVC and advance the care of patients with this specific abnormality, Towbin said.

"We now have the genetic ability � that is, making a diagnosis off of a blood test of the gene � to evaluate these patients from the perspective of the disease's origin," said Towbin. "Hopefully we will be able to engineer new targeted therapies on the basis of these findings."
 

- Journal Circulation Research
 

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Towbin's coauthors include first author Dr. Zhao Yang, of BCM, as well as contributors from Johns Hopkins University, University of Arizona, Harvard Medical School, and the University of Padua in Italy.

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