Publication Date

Spring 2018

School

School of Health Sciences

Major

Biology: Biomedical Sciences

Keywords

HGPS, Progeria, Hutchinson-Gilford Progeria Syndrome

Disciplines

Medical Genetics | Medical Pathology | Medical Sciences | Medicine and Health Sciences

Abstract

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.

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