The surprising discovery, in genetic studies of transparent zebrafish embryos, suggests that the cause of some human congenital heart valve defects may lie not in the genes for the formation of the valve itself, but in genes used in the heart muscle that pumps the blood. About 1,600 valve defects are diagnosed each year in the U.S. and few of the genes responsible for these defects have been identified.

The research team found that a mutation in a single gene involved in heart contraction interfered with the development of the heart valve. While the mutation would kill a human embryo, the discovery shows that normal heart contraction is required for normal valve formation, so even temporary glitches in the early heartbeat might cause valve defects.

"I expected that the early stages of heart valve formation would be completely hard wired, rather than regulated by the beating of the heart," said Didier Stainier, PhD, professor of biochemistry and biophysics at UCSF and senior author of a paper on the discovery published online May 11 by Public Library of Science (PloS) Biology.

"It now seems likely that some heart valve defects in newborn children may be caused by a temporary interruption of normal heart contraction early in the life of the embryo, rather than by genetic defects in the valves themselves. This could lead to a new way to look at congenital heart defects," he said.

If proven true in humans, the finding could allow physicians to treat or prevent heart defects before birth by focusing on fetal heart formation instead of having to cope with the consequences of heart malformations in infants after birth, the researchers said.
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Contact: Wallace Ravven
wravven@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
11-May-2004