Growing up too fast. Normal nuclei are smooth and round, but clipped lamin A (green) results in misshapen nuclei.

A Gene for Growing Old Too Fast

Two groups of researchers have identified the gene responsible for a rare premature aging syndrome whose victims die in their early teens. The finding may help scientists design diagnostic tests and treatments for the disease, and it could provide insights into normal aging processes.

Hutchinson-Gilford progeria syndrome (HGPS) strikes roughly one child in the United States every year. HGPS children grow bald and wrinkled and die of age-related disorders such as heart attacks and strokes due to atherosclerosis. For decades, researchers have been seeking the gene that underlies the disease.

HGPS doesn't run in families, making it extremely difficult to pinpoint the spontaneous mutation that causes it. But Leslie Gordon's research group at Tufts University Medical School in Boston had a clue--a pair of affected identical twins who were each missing a chunk of one chromosome that they had inherited from their father. Mutations in one of the 80 genes found in that region, the LMNA gene, have been fingered in six other genetic diseases.

Joined by Francis Collins, director of the National Human Genome Research Institute, Gordon and colleagues sequenced the LMNA gene in 20 progeria patients. Eighteen of those had a single DNA base switched from the usual cytosine to a thymine. The resulting abnormal protein is the likely culprit, Gordon's team reports online in the 24 April issue of Nature.

A second group of researchers from the University of Marseille in France found the same mutations in two HGPS patients. They too detected the defective protein. The authors postulate that the mutant protein template interferes with the production of the second, healthy copy of the LMNA gene that mothers bequeath to progeria children, they report in the 17 April online issue of Science.

Progeria researcher Marc Lewis of the University of Texas, Austin, speculates that the mutant protein, called lamin A, might be sticking chromosomes to the nuclear wall and preventing genes there from being properly turned on. Gerontologist George Martin of the University of Washington, Seattle, says that the finding provides a "new window" for observing how atherosclerosis might arise.

Related site
Leslie Gordon's Progeria Research Foundation
Francis Collins at the National Genome Research Institute