Stokes Investigators Tackling Mystery Surrounding Ring 20 Abnormalities


A rare but potentially devastating cytogenetic disorder characterized by chromosomes that take a ring-shaped rather than the typical rod-shaped form is at the heart of a new research program by investigators at The Children's Hospital of Philadelphia.

Nancy Spinner, Ph.D., Division of Human Genetics and Molecular Biology, is working with her colleagues to unravel the mysteries surrounding Ring 20 chromosomal abnormalities.

The ring shape makes copying of the chromosomes by the cells difficult and ring chromosomes are associated with clinical abnormalities. Ring 20 chromosomes are most often associated with severe seizures, characterized by specific EEG changes. These seizures do not respond well to medication and are therefore very difficult to control. Development is often normal prior to the onset of the seizures, but becomes abnormal subsequently. Affected individuals generally have cognitive deficits, however these can range from very mild to severe. Abnormalities of other systems are rare in this group of patients.

Dr. Spinner and her colleagues will draw upon their wealth of experience in genetic studies to investigate how the ring chromosome affects gene expression and function. They believe that the abnormal shape of chromosome 20 leads to the deregulation of genes that cause the specific pattern of abnormalities seen in those patients with the disorder.

The preliminary goals of study are to identify patients, collect samples and analyze both DNA and gene expression in patients.

Dr. Spinner and her colleagues will work with the Hospital's Center for Applied Genomics to map these ring chromosomes. Her group will work with the Ring Chromosome 20 Foundation to identify patients and identify additional clinical collaborators. "Understanding the genes involved in Ring 20 chromosome abnormalities will pave the way for future research to study these genes and understand how they lead to the seizures and hopefully, why these seizures are so difficult to control," says Dr. Spinner. "We hope to use this understanding to eventually form the basis of new therapies"

Support for this new research endeavor comes from the Ring Chromosome 20 Foundation, established by the father of a Scottish girl who is affected by the disorder.