Congenital heart disease appears in 1 in 100 births in the United States and is the most common cause of death in childhood. Children with this birth defect face multiple surgeries, a lifetime of medications and various preventive measures to keep their hearts working. But at this time, doctors have no way to permanently fix the hearts of such children.
In treating children with congenital heart disease and related musculoskeletal disorders, Thomas Morgan, M.D., assistant professor of pediatrics and a clinical geneticist, wants to get beyond just relieving symptoms – he wants to find the cause and repair it. Since the causes of congenital heart disease and musculoskeletal defects remain largely unknown, he plans to look for the underlying genetic causes and then tailor a treatment to each patient.
“Right now, surgery is the cornerstone of treatment, but it’s not enough in many cases,” said Morgan, project director. “Gene therapies could complement surgery. This is a gap in knowledge this project will help fill.”
Instead of starting his research in a lab, Morgan will get DNA samples from patients and their families at the St. Louis Children’s Hospital Cardiology Clinic to look for the genetic causes through clues in their DNA. In this bedside-to-bench endeavor, he will be among the first researchers to employ a state-of-the-art technology that uses a “million SNP chip” to analyze the DNA. The chip, created as a result of nanotechnology, uses more than 1 million probes to look for missing pieces of DNA in each patient. Teaming with Washington University’s Division of Genetics and Genomic Medicine and the Genome Sequencing Center, those missing pieces will be compared to the reference human genome. This may reveal genetic variants associated with congenital heart disease and eventually lead to personalized treatment at the patient’s bedside.
“Offering participation in research is part of what caring for children is about,” Morgan said. “Without clinical research like this we have no opportunity to contribute to new knowledge that may help children in the future.”
Previously, geneticists could only analyze 1,500 areas of the genome, which supplied between 5 percent and 10 percent of the causes of congenital heart disease. Using the expanded search, Morgan said the results could unveil many more causes.
“Insights from this analysis may lead to the identification of hard-to-predict genetic pathways that will serve as a foundation for new therapies personalized for the patient,” Morgan said.
Morgan said the ability to so thoroughly analyze each patient’s genetic code would have been considered science fiction a decade ago.
“The ultimate goal is to develop a sophisticated knowledge of what causes congenital heart defects and what targeted therapies would help these children,” Morgan said. “We want to use personalized medicine that targets the one genetic pathway that is known to be disturbed rather than treating the symptom that results.”