The National Institutes of Health (NIH) has awarded Bernice Morrow, Ph.D., at Albert Einstein College of Medicine and collaborators at the Children's Hospital of Philadelphia (CHOP) a five-year, $7.5 million grant to study the genetics of congenital heart abnormalities.
Congenital heart disease affects four of every thousand live births, with most cases due to unknown causes. Dr. Morrow studies the genetics of a rare syndrome usually referred to as 22q11.2 deletion syndrome (22q11.2DS) because affected individuals are missing a portion of chromosome 22. Approximately 60 percent of patients with 22q11.2DS, also known as DiGeorge syndrome and velo-cardio-facial syndrome, have congenital heart disease, mostly of the conotruncal type (i.e., malformations of the cardiac outflow tract), which includes aortic arch anomalies. The deletion also causes several other abnormalities including immune deficiencies, mild craniofacial deformities and behavioral or intellectual disabilities. There is no cure for the disorder.
"One of our major goals is to discover why some individuals with 22q11.2DS have severe disease while others have mild presentations," says Dr. Morrow, director of translational genetics, professor of genetics and the Sidney L. and Miriam K. Olson Chair in Cardiology at Einstein. She also has appointments in obstetrics & gynecology and women's health and in pediatrics. Dr. Morrow and her CHOP collaborators have formed the International 22q11.2 Consortium and an International 22q11.2 Brain Behavior Consortium to increase the number of research samples available for studies of this syndrome. In this particular study, they will compare the genetic findings from patients with 22q11.2DS with those of congenital heart disease patients in the general population, to see if similar genetic risk factors are present in both groups.
Deletion of one particular gene in the deleted 22q11.2 region--TBX1--causes most of the physical abnormalities in the disorder. Those symptoms vary from mild to serious, and Dr. Morrow believes that DNA variations in other genes may influence disease severity. The NIH grant will enable her to track down these "modifier genes" specific for congenital heart disease to see how they interact with each other and with TBX1, using DNA from human subjects and mouse models of 22q11.2DS.
"We hope that this project will greatly expand our understanding of the genetic basis of congenital heart disease and lead to novel therapies and strategies for preventing these defects," she says.
Albert Einstein College of Medicine