Velo-Cardio-Facial Syndrome

Velo-Cardio-Facial Syndrome Research Institute

Project Closed July 2002, research may continue under the Harvard Medical School IRB pending approval.

Description of VCFS Research Project:

MOLECULAR ASPECTS OF THE VELO-CARDIO-FACIAL SYNDROME

In the molecular biology laboratories of Dr. Raju Kucherlapati, Dr. Arthur Skoultchi and Dr. Bernice Morrow at The Albert Einstein College of Medicine efforts to examine the molecular basis of a pair of related human genetic disorders: velo-cardio facial (VCFS) and DiGeorge (DGS) syndromes have been conducted for the past six years. Individuals affected by these disorders have several developmental defects including cardiac anomalies and psychiatric phenotypes. The individuals have a characteristic deletion of a part of human chromosome 22 and it is believed that the presence of a single copy of a gene(s) in this region (haploinsufficiency) causes the disorder. We are utilizing a combination of genetic and molecular biological approaches to identify the gene(s) responsible for these disorders. Rosalie Goldberg a genetic counselor at The Albert Einstein College of Medicine will be happy to answer your questions.

Identification of genes for this disorder provides a unique opportunity to understand the molecular basis for the clinical findings of VCFS and DGS and to gain insight into normal human embryonic development. We have constructed a physical and genetic map of 22q11. By genotyping large numbers of VCFS/DGS patients with genetic markers that have been integrated within the physical map, we have been able to define their deletions. We have isolated several genes within the smallest region of deletion overlap, termed the critical region for VCFS/DGS. A major effort in the lab is to determine the pattern of expression of each gene during embryonic/fetal development as well as in adult tissues.

A second goal is to identify the gene(s) that lead to about 30% susceptibility to the psychiatric disorders and 95% learning disabilities in patients. Seventeen percent of patients with the physical characteristics of VCFS/DGS do not have detectable deletions. We are interested in these subjects to look for smaller deletions or mutations.

The contributions of blood samples from families is essential to our effort to find the gene/genes. Each subject is asked to sign an informed consent and to donate 10 ccs of blood.]

March 4, 1998

We have initiated a new study to determine the mechanism of the deletion on

22q11 causing velo-cardio-facial syndrome and DiGeorge syndrome. The study

involves determining how the two chromosome 22's interacted during the

stage of egg/sperm development termed meiosis. Deficiencies in this

process may result in a deletion or duplication of chromosomal material

(genes). Our goal is to determine why the deletion occurred initially and

to understand the mechanism of chromosome - chromosome interaction during

meiosis. Perhaps we can find methods to prevent it from happening again.

In order to perform our experiments, we need a small amount of blood from

grandparents and parents of the VCFS/DGS patient. The DNA in the

grandparents' blood will enable us to determine how the two chromosome 22's