Genetic Mutations Tied to Progeria Syndrome

About one in 4 to 8 million newborns suffer from Hutchinson-Gilford progeria syndrome, a fatal condition in which children appear healthy at birth but show signs of accelerated aging beginning around age two. These include aged-looking skin, stiff joints, hip dislocation, atherosclerotic heart disease, and hair loss. Children with progeria die at an average age of 13, typically of heart attack or stroke. In the June 15 issue of the Proceedings of the National Academy of Sciences, medical school researcher Robert D. Goldman, PhD, and colleagues described research suggesting that progeria may be caused by mutations of the gene for the lamin A protein that lead to structural and functional defects on the cellular level.

"Although rare, progeria has long been considered a model for studying the mechanisms responsible for normal aging," said Dr. Goldman, Stephen Walter Ranson Professor and chair of cell and molecular biology at the medical school.

Using microscopic and molecular techniques to study cells from children with progeria, Dr. Goldman and colleagues found that as cells aged, defects in the structure and function of cell nuclei increased, reflecting an abnormal accumulation of defective lamin A protein. Lamin A protein's role in cells includes forming a structural scaffolding involved in many aspects of nuclear structure. The protein also is involved in gene expression and DNA replication. Dr. Goldman and colleagues believe that as cells in children with progeria age, their nuclei become progressively more defective, and that the cell function changes that follow can be directly related to the amount of mutant lamin A protein in the cell.