In Progeria patient the cell Nucleushas dramatically abarrant morphology
(bottom right) rather than the uniform
shape typically found in normal cell
Meaning Of Progeria:
The word Progeria comes from the Greek progeros meaning 'prematurely old'. The Greek word pro means 'before', while the word geras means 'old age'. HGPS (Hutchinson-Gilford Progeria Syndrome) or Progeria is an extremely rare, fatal genetic condition. Progeria affects children and gives them an appearance of accelerated aging. The classic type of Progeria (there are different forms) is Hutchinson-Gilford Progeria Syndrome (HGPS). Progeria was first described in an academic journal by Dr. Jonathan Hutchinson in 1886, and Dr. Hastings Gilford in 1897 - both in England.
Epidemiology:
According to Hayley's Page "At present there are 53 known cases of Progeria around the world and only 2 in the UK". There is a reported incidence of Progeria of approximately 1 in every 4 to 8 million newborns. Both boys and girls run an equal risk of having Progeria. Those born with progeria typically live about thirteen years, although many have been known to live into their late teens and early twenties and rare individuals may even reach their forties. 90% of patients die from complications of atherosclerosis, such as heart attack or stroke. Experts do not believe that Progera is hereditary. They say it is due to a rare gene change which happens purely by chance.
Signs & Diagnosis of Progeria:
Children with Progeria are born looking healthy. When they are about 10 to 24 months old, features of accelerated aging start to appear. Signs of Progeria may include:
Growth failure
Loss of body fat
Loss of hair
Skin starts to look aged
Stiffness in the joints
Hip dislocation
Generalized atherosclerosis (cardio and heart disease)
Stroke
A ten-year-old Progeria child will look like an eighty-year-old - but her mind is still that of a ten-year-old.
It can be confirmed through a genetic test
What Gene Say:
HGPS is caused by a mutation in the gene called LMNA (pronounced, lamin - a). The LMNA gene produces the Lamin A protein, which is the structural scaffolding that holds the nucleus of a cell together. Researchers now believe that.it develops during cell division in a newly conceived zygote or in the gametes of one of the parents. It is caused by mutations in the LMNA (lamin A protein) gene on chromosome 1; the defective Lamin A protein makes the nucleus unstable, the mutated form of lamin A is commonly known as progerin.
Introduction of LMNA:
Nuclear lamin A is a protein scaffold on the inner edge of the nucleus that helps organize nuclear processes such as RNA and DNA synthesis.
Prelamin A contains a CAAX box at the C-terminus of the protein (where C is a cysteine and A is any aliphatic amino acids). This ensures that the cysteine is farnesylated and allows prelamin A to bind membranes, specifically the nuclear membrane. After prelamin A has been localized to the cell nuclear membrane, the C-terminal amino acids, including the farnesylated cysteine, are cleaved off by a specific protease. The resulting protein is now lamin A, is no longer membrane-bound, and carries out functions inside the nucleus.
In HGPS, the recognition site that the enzyme requires for cleavage of prelamin A to lamin A is mutated. Lamin A cannot be produced, and prelamin A builds up on the nuclear membrane, causing a characteristic nuclear blebbing.This results in the premature aging symptoms of progeria, although the mechanism connecting the misshapen nucleus to the symptoms is not known.
Treatments:
No treatments have been proven effective. Farnesyltransferase inhibitors (FTIs), currently used for treating cancer, might reverse the nuclear structure abnormalities that are believed to cause Progeria. Studies carried out on mice with Progeria-like signs and symptoms showed that FTIs appeared to offer some improvements. Of the 13 mice treated with FTI, only one died during the 20-week UCLS study. Dr Leslie Gordon, director of the Progeria Research Foundation, said: "This study gives us pieces of information critical to our movement toward clinical trials in children with progeria."
