CHOP, Albert Einstein College of Medicine to study genetics of conotruncal defects

The Eunice Kennedy Shriver National Institute of Child Health & Human Development, part of the National Institutes of Health, has awarded researchers at Albert Einstein College of Medicine of Yeshiva University and collaborators at the Children's Hospital of Philadelphia (CHOP) a five-year, $6.7 million grant to study the genetics of both rare and common congenital heart abnormalities known as conotruncal defects (CTDs).

CTDs account for more than one-third of all heart defects. They can involve a faulty connection between the heart's chambers or an abnormality affecting a major blood vessel leaving the heart. Some of the more common CTDs include ventricular septal defects and tetralogy of Fallot.

"We hope that this project will greatly expand our understanding of the genetic basis of CTDs and lead to novel therapies and preventive strategies for these defects," said principal investigator Bernice Morrow, Ph.D., director of translational genetics, professor of genetics and the Sidney L. and Miriam K. Olson Chair in Cardiology at Einstein. Dr. Morrow has appointments in obstetrics & gynecology and women's health and pediatrics.

The first part of Dr. Morrow's study will examine CTDs occurring in patients with velo-cardio-facial/DiGeorge syndrome, also called 22q11.2 deletion syndrome (22q11DS). The syndrome is caused by the deletion of a small piece of chromosome 22 known as q11.2. This deletion, present in about one in every 4,000 live births, can cause a variety of developmental abnormalities in addition to CTDs, including immune deficiencies, mild craniofacial deformities and behavioral or intellectual disabilities. There is no cure for the disorder. Dr. Morrow and collaborators at CHOP have formed an International 22q11.2 Consortium to greatly expand the number of samples obtained for research.

TBX1, one of the genes in the deleted 22q11.2 region, is largely responsible for the physical abnormalities in the disorder. Since the symptoms of 22q11DS vary from mild to serious, Dr. Morrow believes that DNA variations in other genes may influence disease severity. Her continued research funded by this grant will involve tracking down these "modifier genes" and determining how they interact with each other and with TBX1. She will be using DNAs from human subjects and mouse models of the syndrome in her research.

In another part of the study, the researchers will examine whether genes involved in 22q11DS also play a role in "non-syndromic" CTDs. These defects are more common than the CTDs associated with 22q11DS and thus relevant to a larger number of people.

Source: Albert Einstein College of Medicine of Yeshiva University