The Genetics of Advanced Aging: Hutchinson-Gilford Progeria Syndrome
By: Maxine DrakelyBiological Sciences MajorUniversity of New Hampshire at Manchester


This file is licensed under the Creative Commons Attribution 2.5 Generic and is Public Domain.
This file is licensed under the Creative Commons Attribution 2.5 Generic and is Public Domain.

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic disorder causing rapid premature aging that affects about 1 in 4-8 million children (6). The age of onset is usually within 2 years of life, with death occurring at an average age of 13 as a result of heart attack or stroke (6).

HGPS typically causes symptoms such as:
  • hair loss (alopecia)
  • aged-looking skin
  • joint abnormalities
  • and a loss of fat under the skin

With age, characteristic facial appearances develop and become even more prominent over time. Even more so than those seen on the child in the photograph above.

The photograph also shows a cellular characteristic of the disease which is found in the cells nucleus'. The top-right photo depicts a cell nucleus with a uniform shape that is typically found in healthy individuals. The bottom-right photo however, shows an abnormal morphology revealing the havoc this disorder wrecks on the cell nucleus of an HGPS patient.

Fortunately, studies of HGPS have become very common throughout the years in an effort to help prevent and treat the disorder. One particular study published a paper titled, "The Role of Progerin-Induced Telomere Dysfuntion in HGPS Premature Cellular Senescence" in which they discussed the syndrome from a genetic standpoint. The authors explained how HGPS is caused by a silent mutation within the LMNA gene that encodes lamin A (6). This mutation exposes a cryptic splice in exon 11 that leads to the deletion of 50 amino acids required for normal lamin A processing, resulting in an abnormal and permanently farnesylated lamin A protein called progerin (6). It was also noted the condition is autosomal dominant indicating there is one copy of a mutant gene and one copy of a normal gene on a pair of autosomal chromosomes (chromosomes that are not sex chromosomes)(1).

In an effort to understand the genetics of advance aging more in depth, in particular Hutchinson-Gilford Progeria Syndrome, a closer look into the LMNA gene and it's HGPS inducing mutation was conducted and broken down into more manageable parts. After reading these parts you should be able to understand some if not all of the genetic fundamentals underlying the disorder along with it's treatment.


What is the LMNA Gene? >>



(1) Genetics Home Reference (2007). Hutchinson-Gilford Progeria Syndrome. Retrieved from http://ghr.nlm.nih.gov/condition/hutchinson-gilford-progeria-syndrome.
(2) MedicineNet (2011). Definition of Autosomal Dominant. Retrieved from http://www.medterms.com/script/main/art.asp?articlekey=11974.
(6) Aaronson, S., Benson, E., Lee, S. (2010). Role of Progerin-Induced Telomere Dysfunction in HGPS Premature cellular senescence.Retrieved from http://jcs.biologists.org/content/123/15/2605.full