Cincinnati Children's Identifies Genes Linked to Congenital Heart Condition in Children
Cincinnati Children's Hospital Medical Center has identified mutations in three genes of children born with a heart condition that interferes with regular beating of the heart.
WASHINGTON (PRWEB) June 12, 2004
A scientist at Cincinnati Children's Hospital Medical Center has identified mutations in three genes of children born with a heart condition (http://www. cincinnatichildrens. org/health/heart-encyclopedia/default. htm (http://www. cincinnatichildrens. org/health/heart-encyclopedia/default. htm)) that interferes with regular beating of the heart.
This new discovery increases the understanding of the genetic basis of atrioventricular (AV) conduction disease and offers the promise of improved diagnosis and screening, as well as new strategies for treatment.
The discovery "helps explain some of the mysteries of AV conduction disease in children, such as why problems sometimes don't show up until the child is much older," says D. Woodrow Benson, MD, PhD (http://www. cincinnatichildrens. org/svc/staff/b/woodrow-benson. htm (http://www. cincinnatichildrens. org/svc/staff/b/woodrow-benson. htm)), a cardiologist (http://www. cincinnatichildrens. org/svc/prog/heart/clinical/cardiology. htm (http://www. cincinnatichildrens. org/svc/prog/heart/clinical/cardiology. htm)) at Cincinnati Children's who led the study. Dr. Benson will present the study Monday, April 19 at Experimental Biology 2004, as part of the scientific sessions of the American Association of Anatomists in Washington, DC.
For some children, AV conduction disease is associated with such congenital heart problems as cardiac malformation or cardiomyopathy (http://www. cincinnatichildrens. org/health/heart-encyclopedia/disease/cardiomyopathy. htm (http://www. cincinnatichildrens. org/health/heart-encyclopedia/disease/cardiomyopathy. htm)), or with certain neuromuscular diseases. In some children, the cause of AV conduction disease is unknown.
Several studies at Cincinnati Children's and elsewhere have identified AV conduction disease in familial clusters over multiple generations, suggesting a genetic cause in these children with no other associated disease. Wanting to determine the specific genes involved, Dr. Benson's lab enlisted the help of nearly 50 patients at Cincinnati Children's, from newborns to 20-year-olds, and the DNA of their family members.
Dr. Benson and his colleagues compared the sequence of genes in these families to the normal sequence of genes in the human genome. They found differences in genes with three different functions in the heart: excitability, energy and transcription (the regulation of other genes). Armed with this knowledge, the researchers are able to trace the fingerprints of the three genes on physical history and particular features in electrocardiograms.
They now are looking for new ways to use this information to know which children are at risk for a condition that has plagued other family members, when the disease is likely to cause problems, and what types and how severe such problems may be. Differences in which gene is causing the problems also are likely to suggest differences in treatment, says Dr. Benson.
Dr. Benson also examined mouse models of AV conduction disease and discovered that some of the missing genes were also abnormal in the Cincinnati Children's patients.
Currently the youngest children with AV conduction disease usually receive the same treatment as do the oldest adults with electrophysiological problems: a pacemaker, which, like car batteries, needs to be replaced at regular intervals. Most older adults receive pacemakers after their heart tissue has been injured by heart attack or disease. But for the small percentage of pacemaker wearers in the United States under the age of 20, only a very few have experienced such injury.
Although AV conduction disease is relatively rare, Dr. Benson hopes his research will have implications for other diseases of the heart that show up later in life but have origins in childhood.
Jim Feuer, 513-636-4656, jim. feuer@cchmc. org
