Progeria Essay

Progeria, meaning "before" or "premature", and "gēras", meaning "old age". The disorder has a very low incidence rate, occurring in an estimated 1 per 8 million live births. Those born with progeria typically live to their mid teens to early twenties. It is a genetic condition that occurs as a new mutation, and is rarely inherited, as carriers usually do not live to reproduce. Although the term progeria applies strictly speaking to all diseases characterized by premature aging symptoms, and is often used as such, it is often applied specifically in reference to Hutchinson–Gilford progeria syndrome .
Scientists are particularly interested in progeria because it might reveal clues about the normal process of aging. Progeria was first described
in 1886 by Jonathan Hutchinson. It was also described independently in 1897 by Hastings Gilford. The condition was later named Hutchinson–Gilford progeria syndrome.
Signs and symptoms
Children with progeria usually develop the first symptoms during their first few months of life.
The earliest symptoms may include a failure to thrive and a localized scleroderma-like skin condition. As a child ages past infancy, additional conditions become apparent usually around 18–24 months. Limited growth, full-body alopecia, and a distinctive appearance are all characteristics of progeria. Signs and symptoms of this progressive disease tend to become more marked as the child ages. Later, the condition causes wrinkled skin, atherosclerosis, kidney failure, loss of eyesight, and cardiovascular problems. Scleroderma, a hardening and tightening of the skin on trunk and extremities of the body, is prevalent. People diagnosed with this disorder usually have small, fragile bodies, like those of elderly people. The face is usually wrinkled, with a larger head in relation to the body, a narrow face and a beak nose. Prominent scalp veins are noticeable, as well as prominent eyes. Musculoskeletal degeneration causes loss of body fat and muscle, stiff joints, hip dislocations, and other symptoms generally absent in the non-elderly population. Individuals usually retain typical mental and motor
development.
Cause
In normal conditions, the LMNA gene codes for a structural protein called prelamin A which undergoes a series of processing steps before becoming its final form, called lamin A. In one of these steps, after prelamin A is made in the cytoplasm, an enzyme called farnesyl transferase attaches a farnesyl functional group to its carboxyl-terminus. The farnesylated prelamin A is then transported through a nuclear pore to the interior of the nucleus. The farnesyl group allows prelamin A to attach temporarily to the nuclear rim. Once the protein is attached, it is cleaved by a protease, thereby removing the farnesyl group along with a few adjacent amino acids. Failure to remove this farnesyl group permanently affixes the protein to the nuclear rim. After cleavage by the protease, prelamin A is referred to as lamin A. Lamin A, along with lamin B and lamin C, makes up the nuclear lamina, which provides structural support to the nucleus.
Before the late 20th century, research on progeria yielded very little information about the syndrome.
In 2003, the cause of progeria was discovered to be a point mutation in position 1824 of the LMNA gene, in which cytosine is replaced with thymine. This mutation creates a 5' cryptic splice site within exon 11, min A protein whose farnesyl group cannot be removed. Because its farnesyl group cannot be removed, this abnormal protein, referred to as progerin, is permanently affixed to the nuclear rim, and therefore does not become part of the nuclear lamina. Without lamin A, the nuclear lamina is unable to provide the nuclear envelope with adequate structural support, causing it to take on an abnormal shape. Since the support that the nuclear lamina normally provides is necresulting in an abnormally short mature mRNA transcript. This mRNA strand, when translated, yields an abnormal variant of the
prela