Werner Syndrome Health Article

Definition

Werner syndrome is a very rare, inherited disease that resembles premature aging. Since the gene responsible was discovered in the mid-1990s, Werner syndrome has greatly interested researchers as a possible model for the study of human aging. It is also being extensively studied for insights it may eventually supply into a number of other diseases including cancer, diabetes mellitus, and atherosclerosis.

Description

This syndrome is named for the German physician C. W. Otto Werner (1879-1936). Werner was a medical student in 1903 when he first observed the syndrome in four siblings, all about 30 years of age. The following year, Werner wrote about these observations in his "Inaugural Dissertation."

The clinical signs and symptoms of Werner syndrome start to appear during the teen or early adult years, after which patients appear to age rapidly and have a greater-than-usual chance of developing cancer, cardiovascular disease, or diabetes mellitus. By the time the patient is 30–40 years old, he or she has the look of old age. The most common cause of death is heart attack.

While in many ways the signs and symptoms of Werner syndrome resemble those of premature aging (referred to in adults as progeria), there are also some significant differences. For instance, the tumors commonly seen in Werner syndrome patients are commonly derived from the cells of the mesoderm, a middle layer of the embryo that gives rise to a variety of tissues including cartilage, muscle, bone, kidneys, and connective tissue. In normal aging, tumors are more likely to be derived from the epithelial cells that cover the body's exterior and line most of its hollow structures. Osteoporosis and soft-tissue calcium deposits are found both in Werner syndrome and normal aging, but the distribution of these conditions within the body is different in patients with Werner syndrome. In addition, patients with Werner syndrome do not generally experience symptoms of Alzheimer disease or premature cognitive decline, as do their aging counterparts in the general population.

Researchers are uncertain whether the symptoms of Werner syndrome are really a speeding-up of normal aging, or whether the many similarities are coincidental. There is nonetheless considerable optimism that further research into Werner syndrome may lead to a better understanding of aging, cancer, diabetes, systemic sclerosis, atherosclerosis, cataracts, and other conditions.

Genetic profile

Werner syndrome results from mutation of a single gene. In 1992, the gene responsible (WRN) was mapped to chromosome 8p11-12. In 1996, a research group based in Seattle cloned the WRN gene. It was also discovered that the syndrome resulted from an autosomal recessive mutation that affects a member of a family of enzymes known as helicases that unwind deoxyribonucleic acid (DNA) and, in some cases, ribonucleic acid (RNA).

Despite the discovery that Werner syndrome is caused by a genetic defect, researchers are unable to explain exactly how this defect causes the disease. The purpose of helicases in the body is not fully understood, but they are known to unwind DNA, splitting the double-stranded molecules into separate single-stranded molecules. In this way, the enzymes are involved in the repair, recombination, replication, and transcription of DNA. There appear to be many damaged sites in DNA taken from patients with Werner syndrome. It has therefore been suggested that Werner syndrome may be caused by failure in these DNA-related processes, and that the somatic cells of those with Werner syndrome may be particularly prone to mutations.

The WRN gene is not known to bind to DNA damage, but recent research has suggested it might be able to sense the presence of damaged DNA. Since the discovery of the WRN gene, more than 10 mutations have been uncovered. Many of these mutations were in the Japanese population. It has been suggested that the relatively high incidence of Werner syndrome in that country may be related to traditions of marriages between closely related individuals in some areas of Japan.

Researchers are seeking an animal model to allow them to further study Werner syndrome. Specifically, they hoped to create mice with a genetic equivalent of the WRN gene, and to determine whether these mice would age more quickly than normal mice.