A mutation of the gene for lamin A protein gradually causes devastating effects on cellular structure and function in Hutchinson-Gilford progeria syndrome, a rare, fatal genetic condition characterized by an appearance of accelerated aging in children.
A study on the lamin A gene mutation was published in this week’s Proceedings of the National Academy of Sciences.
“Although a rare disease, progeria has long been considered a model for studying the mechanisms responsible for normal aging,” said lead author Robert D. Goldman, Stephen Walter Ranson Professor and chair, cell and molecular biology at Northwestern University Feinberg School of Medicine.
Goldman, a noted expert on the cell’s nuclear architecture, explained that lamin A protein forms a structural scaffolding that is responsible for many aspects of nuclear structure, and it is involved in gene expression and DNA replication.
Earlier research found that progeria is caused by mutations of the lamin A gene. The PNAS study, by scientists from Northwestern University, the Progeria Research Foundation and the National Institutes of Health, used microscopic and molecular techniques to examine nuclear structural changes of cells from children with progeria.
The researchers found that as the progeria cells aged, there was a gradual increase in defects in the nuclear structure and function, reflecting an abnormal accumulation of the defective lamin A protein. Very similar changes were seen in the nuclei of normal human cells from both children and elderly persons treated with the mutated lamin A gene.
Goldman and colleagues believe that as progeria cells age and their nuclei become progressively more defective, there are significant changes in cell function that are directly attributable to the amount of mutant lamin A protein.
“These findings strengthen our suspicions that instability of the cell’s nuclear envelope plays a key role in Hutchinson-Gilford progeria syndrome,” said Francis S. Collins, M.D., one of the senior authors on the study and director of the National Human Genome Research Institute.
“We now know far more about how one tiny genetic mutation can lead to a situation in which the cell’s architecture is severely and progressively damaged,” Collins said.