The Genetics of Progeria: a Rare Genetic Disorder

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What is Progeria?

The National Human Genome Research Institute defines progeria (Hutchinson-Gilford progeria syndrome - HGPS) as “an extremely rare genetic disease of childhood characterized by dramatic, premature aging.”. In fact, the disease is so rare that it has been estimated that only one in 4 million newborns is affected by progeria (Hennekam, 2006).

Newborns affected by this disease have a normal appearance upon birth. The first symptoms appears as the child grows as a failure to thrive, having less body weight and shorter stature than children of the same age. Other signs of the disease start to appear as the child grows: baldness, prominent eyes, micrognathia (small lower jaw), high-pitched voice, delayed and abnormal tooth formation, skin that wrinkles and looks as that of an old person, small face, and a large head size. Other health related problems, usually seen in older people, appear very early in progeria patients: hip dislocation, bone fragility, osteoarthritis, cardiovascular disease, etc.

The Genetics of Progeria

Progeria is a genetic disease. It is caused by a simple tiny point mutation in a single gene. The gene is called the LMNA or Lamin A gene. The point mutation (single base substitution) occur at position 1824 of the DNA chain. A cytosine nucleotide is replaced by a thymine nucleotide, creating an unusable form of the protein Lamin A (coded by the gene LMNA).

Progeria is an example of how a simple genetic change (onle one nucleotide base of the 25000 that the gene has) can have a tremendously deleterious effect on the human being. Parents of children with progeria are not affected by the disease. The mutation of the LMNA gene occurs prior to conception in the father’s sperm. The disease, although rare, is extremely important for research because it can give clues to science about the mechanism of aging.

Lamin A plays a key role in stabilizing the inner membrane of the cell’s nucleus. The abnormal Lamin A protein produced by the affected gene seem to destabilize the cell’s membrane of the nucleus. The net effect of this destabilization is a deleterious effect on tissues associated with physical force such as bones, connective tissue, muscles (including the heart muscle).

Is there Any Treatment for Progeria?

Unfortunately, progeria is incurable. At least 90% of patients die from complications such as atherosclerosis, heart attack or stroke, at an early age (not more than 13 years).

The available treatments are geared towards attacking signs and symptoms that may compromise the life of the patient. Cardiovascular problems are usual in progeria patients so treatments are available. Heart by-pass is usually performed in progeria patients.


National Human Genome Research Institute:

Hennekam RC (2006). “Hutchinson-Gilford progeria syndrome: review of the phenotype”. Am. J. Med. Genet. A 140 (23): 2603–24.

The Genetics of Progeria. Mayo Clinic.