Progeria

By Michael Du

Soo, what is Progeria?
It is an extremely rare genetic condition
where symptoms of aging manifest itself at
an early age.
It is estimated to occur in 1 in 8 million live
births.
Those with Progeria typically live to their
mid teens or early twenties.
Cause
Progeria is caused by a point mutation in
position 1824 of the LMNA gene on
chromosome 1, with a cytosine being
replaced by a thymine (GGC>GGT). This
creates a truncated form of the protein
prelamin A, called progerin.
The mutation takes place in either the
parent gametes or in the fertilised egg
itself. The disease is rarely inherited.
A more in depth look






Structural nuclear membrane
abnormalities in progeria
Erikkson et al. Nature 2003
Recurrent de novo point mutations in lamin A cause
HutchinsonGilford progeria syndrome
Normal mother
Progeria child
Mice carrying LMNA mutation display progeria
syndrome
Mounkes et al. Nature 2003
A progeroid syndrome in mice is caused by defect in A-type lamins
Normal mouse
lifespan:
approxi. 800 days
Nuclear abnormalities in cells from old individuals
Healthy young Healthy aged Progeria
Lamin A-Dependent Nuclear Defects in Human Aging
Scaffidi et al. Science 2005
-same molecular mechanism responsible for HGPS is active in healthy cells during aging
Treatment
There is no cure for this illness and most treatments are
ineffective.
A type of anti-cancer drug, called the farnesyltransferase
inhibitors, have been proposed but their use has been
mostly limited to animal models. A phase II clinical trial
using the FTI Inofarnib began in May 2007.
Another anti-cancer drug rapamycin caused removal of
progerin from the nuclear membrane through autophagy.
Other drugs have also shown to be able to block farnesyl
group production.
However, it is important to remember that no treatment
can cure Progeria.
The End
Questions?