School of Health Sciences
Biology: Biomedical Sciences
HGPS, Progeria, Hutchinson-Gilford Progeria Syndrome
Medical Genetics | Medical Pathology | Medical Sciences | Medicine and Health Sciences
Eschedor, Danielle M., "Hutchinson-Gilford Progeria Syndrome Vascular Pathology: A Focused Review" (2018). Senior Honors Theses. 776.
Hutchinson-Gilford Progeria is an accelerated aging disorder caused by a de novo point mutation in the LMNA gene which codes for an intermediate filament of the nuclear lamina called lamin A. The point mutation at c.1824C>T causes a 50-amino-acid deletion that removes the binding site for Zmpste24, a metalloprotease responsible for defarnesylating prelamin A and producing mature lamin A. Without the ability to be defarnesylated, the mutated protein, called progerin, is more lipophilic and has a myriad of cytotoxic effects. As cardiovascular disease is the most common cause of death in HGPS patients, it is important for both healthcare professionals and the scientific community to understand how the cellular pathologies induced by progerin contribute to vascular pathology. This review identified four categories of vascular pathology and explains the cellular pathologies that contribute to them. These categories are vascular smooth muscle cell (VSMC) loss and lack of replenishment, vascular calcification, atherosclerosis, and contractility. It also addresses relevant treatment options for patients with the disease.