Congenital heart disease is the most common birth defect in the U.S. that increases morbidity and mortality in children as well as adults. The latest research suggests that genetic mutations may play a significant role in the pathogenesis of some congenital heart diseases. Senior author of the new study, Vidu Garg (who is also principal investigator at the Center for Cardiovascular and Pulmonary Research and director of Translational Research in The Heart Center at Nationwide Children’s) commented:
“We have to ask ourselves, what subset of the more than 20,000 genes that make up the human genome are contributing to congenital heart disease? Right now, we don’t know enough about a lot of those genes, so this study provides another piece of the puzzle.”
Garg suggested that since several hundred genes contribute to the development of the heart, it is definitely a major challenge to identify a particular genetic mutation that may lead to congenital heart disease.
The researchers from the Research Institute at Nationwide Children’s Hospital, expect to narrow down the genes that may cause a particular genetic defect that is responsible for congenital heart disease in as many as 40,000 newborns a year. The results of this study have been published recently in the scientific journal Human Mutation.
The regulation of normal tissue development throughout the body (which includes heart, lung and brain) is controlled by a large gene family. One of the most important genes that are required for the normal development of the heart is FOXP1. Dr, Garg decided to study FOXP1 in detail after a former colleague from the University of Texas Southwestern Medical Center discussed an interesting case involving the same gene.
University of Texas Southwestern Medical Center researcher Dr. Linda Baker analyzed the DNA sample from an 8 month-old infant who died from complications of complex congenital heart disease. Linda identified a small chromosomal deletion — a rare genetic abnormality in the patient’s FOXP1 gene. A number of studies have previously described the essential role and function of FOXP1 in cardiac development in animal models.
To further study the gene in detail, the research team studied the DNA samples from one of the largest repositories at Nationwide Children’s, which revealed two additional patients with the rare mutation in the same gene and similar pattern of cardiac defects. The research team concluded that the mutation of the affected gene interferes with the expression of a transcription factor called Nkx2.5, leading to development of a cardiac defect.
Dr. Garg, (also an associate professor of pediatrics at The Ohio State University College of Medicine) explained:
“If you have three unrelated people with an abnormality in the same gene with the same phenotype, and they also have the same extremely rare type of congenital heart disease, there’s a high likelihood that the gene is involved in contributing to the condition. Understanding how either deletion or loss of FOXP1 affects normal heart development could help contribute to our understanding of congenital heart disease.”
Garg and his team is now working to identify if patients with other types of congenital heart defects may also have mutations in theFOXP1 gene. This may help in identifying other genes too that may contribute to other types of congenital heart defects.
Photo from chop.edu.