Hutchinson Gilford Progeria Syndrome; Epidemiology, Causes, Cellular Mechanisms, Diagnosis, Complications and Advanced Treatment

Progeria is a rare genetic disorder that causes premature ageing. It affects the skin, bones, heart, and blood vessels. HGPS usually results from a new point mutation in the LMNA gene, which leads to an alternative splicing defect and produces the mutant protein, progerin. Progerin acts in a dominant-negative way, resulting in various changes at the cellular and molecular levels. These changes include nuclear abnormalities, problems with the DNA damage response, issues with DNA repair, and faster telomere shortening. Interestingly, many signs of HGPS cells resemble those of normal ageing cells. The LMNA mutation leads to the buildup of LMNA which triggers arteriosclerosis, osteoporosis, and cardiovascular problems like heart attacks and strokes. Children with HGPS seem normal at birth but show growth failure by 6-24 months. They experience dwarfism, hair loss, an aged facial appearance (small face, large eyes, beaked nose), prominent scalp veins, skin tightening, joint stiffness, dental crowding, and hearing loss, all while their cognitive development remains normal. This article discussed the current understanding of the molecular pathways that contribute to the pathophysiology of HGPS. It also covers the techniques being tested both in lab settings and in live models to reduce progerin toxicity. Moreover, HGPS cells and preclinical animal models have provided new insights into the disease’s molecular and cellular pathways, as well as potential mechanisms related to normal aging. This article explores how progerin expression leads to HGPS and how the cellular mechanisms and new treatment options for HGPS patients can improve our understanding and management of this condition.