Werner's syndrome

Werner syndrome is a very rare, autosomal recessive disorder whose most recognizable characteristic is premature aging. Werner's syndrome more closely resembles "accelerated aging" than any other "segmental progeria". For this reason, Werner syndrome is often referred to as a progeroid syndrome, as it partly mimics the symptoms of Progeria. The defect is on a gene that codes DNA helicase and it is located on the short arm of the 8th chromosome. As a result DNA replication is impaired in this syndrome. This condition is inherited in an autosomal recessive pattern. more...

Symptoms

Individuals with this syndrome typically grow and develop normally until they reach puberty. Following puberty, they age rapidly, so that by the time they reach age 40 they often appear as though they are several decades older. The age of onset of Werner syndrome is variable, but an early sign is the lack of a teenage growth spurt, which results in short stature. Other signs and symptoms appear when affected individuals are in their twenties or thirties and include loss and graying of hair, hoarseness, thickening of the skin, and cloudy lenses (cataracts) in both eyes. Overall, people affected by Werner syndrome have thin arms and legs and a thick trunk. Affected individuals typically have a characteristic facial appearance described as "bird-like" by the time they reach their thirties. Patients with Werner sydrome also exhibit genomic instability, hypogonadism, and various age-associated disorders; these include cancer, heart disease, atherosclerosis, diabetes mellitus, and cataracts. However, not all characteristics of old-age are present in Werner patients; for instance, senility is not seen in individuals with Werner syndrome. People affected by Werner syndrome usually live into their late forties or early fifties, death often result from cancer or heart disease.

Epidemiology

Werner syndrome is an exceedingly rare disorder, with some estimates suggesting that it afflicts approximately 1 in 1,000,000 individuals worldwide. Werner syndrome is estimated to affect 1 in 200,000 individuals in the United States. In Japan, the syndrome occurs more often, affecting between 1 in 20,000 and 1 in 40,000 people.

Genetics

In 1996 the gene responsible for Werner syndrome was identified (and named WRN) and found to be a member of the RecQ family of helicases. Other members of this family include the genes responsible for Bloom syndrome (BLM gene), and a subset of Rothmund-Thomson (RECQ4 gene) patients. The Werner protein is thought to perform several tasks in the cell, including the maintenance and repair of DNA. It also assists in making copies of DNA in preparation for cell division. Mutations in the WRN gene often lead to the production of an abnormally short Werner protein. Some research suggests that this shortened protein is not sent to the nucleus, where it normally interacts with DNA. Evidence also suggests that the altered protein is broken down quickly in the cell, leading to a loss of Werner protein function

Research into the biological role of the WRN protein is ongoing, but current evidence strongly suggests a role for WRN in the resolution of Holliday junctions. Roles in non-homologous end joining (NHEJ) and the restoration of stalled replication forks have also been suggested.

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