Progeria

Mutations in the LMNA gene cause Hutchinson-Gilford progeria syndrome.

The LMNA gene provides instructions for making a protein called lamin A. This protein plays an important role in determining the shape of the nucleus within cells. It is an essential scaffolding (supporting) component of the nuclear envelope, which is the membrane that surrounds the nucleus. Mutations that cause Hutchinson-Gilford progeria syndrome result in the production of an abnormal version of the lamin A protein. The altered protein makes the nuclear envelope unstable and progressively damages the nucleus, making cells more likely to die prematurely. Researchers are working to determine how these changes lead to the characteristic features of Hutchinson-Gilford progeria syndrome.

Progeria is a rare condition characterized by dramatic, rapid aging beginning in childhood. Affected newborns usually appear normal but within a year, their growth rate slows significantly. Affected children develop a distinctive appearance characterized by baldness, aged-looking skin, a pinched nose, and a small face and jaw relative to head size. They also often have symptoms typically seen in much older people including joint stiffness, hip dislocations and severe, progressive cardiovascular disease. Intelligence is typically normal. The average lifespan is age 13-14; death is usually due to heart attack or stroke. Progeria is caused by mutations in the LMNA gene, but almost always results from a new mutation rather than being inherited from a parent. Management focuses on the individual signs and symptoms of the condition. Although there is currently no cure, research involving treatment is ongoing and progress is being made.

The LMNA gene is located on the long (q) arm of chromosome 1 at position 22. More precisely, the LMNA gene is located from base pair 156, 082,545 to base pair 156,140,088 on chromosome 1.

Click here to view an image depicting the location of the LMNA gene.

Progeria is very rare. It is reported to occur in 1 in 4-8 million newborns worldwide. It is estimated that at any one time, there are between 200-250 children living with progeria.

Management for progeria generally focuses on the signs and symptoms of the condition and may include the following:

• Exercise, diet modification, and medication when the lipid profile becomes abnormal
• Frequent small meals to maximize caloric intake
• Oral hydration
• Use of shoe pads for foot discomfort due to lack of body fat
• Use of sunscreen on all exposed areas of skin
• Nitroglycerin for angina
• Routine anticongestive therapy if congestive heart failure is present
• Statins for their putative effect on farnesylation inhibition
• Anticoagulation therapy if vascular blockage, transient ischemic attacks, stroke, angina, or heart attack occur
• Routine physical and occupational therapy to help maintain range of motion in large and small joints

Although there is currently no cure for progeria, research involving treatments is ongoing and scientists have been making much progress. The results of a recently published phase II clinical trial provided preliminary evidence that lonafarnib, a farnesyltransferase inhibitor, may improve cardiovascular status, bone structure, and audiological (hearing) status in affected children. A free, full-text version of this study is available on PubMed and can be viewed by clicking here.