A gene known to be important in cardiac development has been newly associated with congenital heart malformations that result in obstruction of the left ventricular outflow tract.
Left ventricular outflow tract (LVOT) malformations is responsible for a major portion of childhood death from congenital heart malformations.
To identify specific genes, investigators examined the DNA of children treated for LVOT malformations and their parents, enrolled by Dr. McBride at Nationwide Children's Hospital or by Dr. John Belmont and his team in the Department of Molecular and Human Genetics, Baylor College of Medicine at Texas Children's Hospital.
Research indicated that LVOT defects share a common developmental mechanism, thus they focused on genes from a signalling pathway shown to be important in cardiac development.
Findings showed an association between the gene ERBB4 and LVOT defects. ERBB4 encodes a protein that serves as an "on" or "off" switch in many cellular functions during heart development. The association with LVOT defects was noted not only for the whole group of defects, but also individually for aortic valve stenosis, coarctation of the aorta and hypoplastic left heart syndrome.
"The precise defect in this very large gene is not yet known," said one of the study's authors Kim McBride, principal investigator in the Center for Molecular and Human Genetics at The Research Institute at Nationwide Children's Hospital.
"ERBB4 now joins a previously identified gene, NOTCH1, as a susceptibility gene for LVOT defects. Replication of these results in other subjects will be required to better determine its role in the development of the heart malformations," added McBride.
The study has been published in the journal Birth Defects Research Part A.