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CHOP Researcher Helps Discover a Cause for Abnormal Heart Vessels

Published on August 8, 2013 in Cornerstone Blog · Last updated 3 months 4 weeks ago


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A pediatric cardiologist at The Children’s Hospital of Philadelphia is a first author of new research identifying a mutation that disrupts the formation of veins bringing blood to the heart very early in development. The abnormal connections and blood flow result in so-called “blue babies” — newborns with a potentially deadly heart condition.

Karl Degenhardt, MD, PhD, of the Cardiac Center at Children’s Hospital, is one of three co-first authors of a study published May 12 in the prestigious journal Nature Medicine. The study leader and senior author is Jonathan A. Epstein, M.D., chair of Cell and Developmental Biology at the Perelman School of Medicine at the University of Pennsylvania.

The researchers analyzed the congenital condition called total anomalous pulmonary venous connection (TAPVC), in which pulmonary veins fail to connect normally to the heart’s left atrium. Because these veins carry oxygen-rich blood from the lungs, this faulty connection means that blood circulating to the body carries insufficient oxygen — hence the blue skin color in newborns with this condition.

Working in animal models, the study team focused on a mouse gene that produces a key signaling protein called Sema3d. When a mutation disrupts normal biological signals, blood vessels form in the wrong location and the circulation goes seriously astray. The researchers then analyzed DNA from 40 CHOP patients with this TAPVC and a related milder condition, and found a mutation in the human gene that corresponds to those studied in mice.

“Although further studies need to be done, this research shows a new mechanism for how a particular gene mutation may cause this important congenital heart condition in children,” said Dr. Degenhardt. While the study does not immediately affect treatment, it may provide a starting point for future therapies targeting the specific gene or signaling pathway.

The authors also point out that further research on the same signaling genes and proteins may suggest treatments for other diseases involving blood circulation, including cancers, retinal disorders and vascular conditions.