Werner Syndrome
Return to Library
What is Werner syndrome?
Werner syndrome is a rare disorder characterized by the dramatic, rapid appearance of aging. Individuals with this syndrome typically grow and develop normally until they reach puberty. 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. As the syndrome progresses, affected people may experience additional skin problems, type 2 diabetes, diminished fertility, severe hardening of the arteries (arteriosclerosis), thinning bones (osteoporosis), and some types of cancer. Affected individuals typically have a characteristic facial appearance described as bird-like by the time they reach their thirties. People affected by Werner syndrome usually live into their late forties or early fifties.
How common is Werner syndrome?
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.
What genes are related to Werner syndrome?
Mutations in the WRN gene cause Werner syndrome.
The WRN gene provides instructions for the production of Werner protein. This 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 (replication) 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. Researchers do not fully understand how WRN mutations cause this syndrome. Cells with an altered Werner protein may divide less often than normal, leading to growth failure. Also, the altered protein may allow DNA damage to accumulate, which could impair normal cell activities and cause health problems related to this condition.
How do people inherit Werner syndrome?
This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder each carry one copy of the altered gene but do not show signs and symptoms of the disorder.
Source: National Institutes of Health
|
Free Werner Syndrome Articles |
|
|
|
|
Reports outline cancer study results from J. Dejmek et al
2009 JUN 22 - (NewsRx.com) -- "Both the Ku subunit of the DNA-dependent protein kinase (DNA-PK) and the facilitator of chromatin transcription (FACT) complex reportedly bind cisplatin-DNA adducts. For this study, we developed an immunocytochemical assay based on detergent extraction allowing unveiling nucleolar subpopulations of proteins present in both the nucleoplasm and the nucleolus," scientists in the United States report. "Immunofluorescence analysis in various human cancer cell lines and immunoblotting of isolated nucleoli show that DNA-PK catalytic subunit (DNA-PKcs), Ku86, the Werner syndrome protein (WRN), and the structure-specific recognition protein 1 (SSRP1) subunit of FACT colocalize in the nucleolus and exit the nucleolus after cisplatin treatment. Nucleolar localization of Ku is also lost after y or UV irradiation and exposure to DNA-damaging drugs, such as actinomycin D, mitomycin C, hydroxyurea, and doxorubicin. Ku86 and WRN leave the nucleolus after exposure to low (>1 mu g/mL) doses of cisplatin. In contrast, the SSRP1 association with the nucleolus was disrupted only by high (50-100 mu g/mL) doses of cisplatin. Both cisplatin-induced loss of nucleolar SSRP1 and DNA-PK activation are suppressed by pretreatment of the cells with wortmannin or the DNA-PK inhibitor NU7026 but not by the phosphatidylinositol 3-kinase inhibitor LY294002. In the same conditions, kinase inhibitors did not alter the exit of DNA-PKcs and WRN, suggesting that different mechanisms regulate the exit of DNA-PK/WRN and FACT from the nucleolus. Furthermore, RNA silencing of DNA-PKcs blocked the cisplatin-induced exit of nucleolar SSRP1," wrote J. Dejmek and colleagues. The researchers concluded: "Finally, silencing of DNA-PKcs or SSRP1 by short hairpin RNA significantly increased the sensitivity of cancer cells to cisplatin. (Mol Cancer Res 2009;7(4):581-91)'." Dejmek and colleagues published their study in Molecular Cancer Research (DNA-Dependent Protein Kinase (DNA-PK)-Dependent Cisplatin-Induced Loss of Nucleolar Facilitator of Chromatin Transcription (FACT) and Regulation of Cisplatin Sensitivity by DNA-PK and FACT. Molecular Cancer Research, 2009;7(4):581-591). For more information, contact J.B. Lazaro, Dana Farber Cancer Institute, Dept. of Cancer Biology, 44 Binney St., Smith 1058, Boston, MA 02115, USA. Publisher contact information for the journal Molecular Cancer Research is: American Association Cancer Research, 615 Chestnut St., 17TH Floor, Philadelphia, PA 19106-4404, USA. Keywords: United States, Smith, Cancer, Cancer Research, Cisplatin, DNA, Diagnosis, Diagnostics, Doxorubicin Hydrochloride, Drugs, Enzyme Research, Hydroxyurea, Kinase, Mitomycin, Oncology, Pharmaceuticals, Therapy, Treatment, Werner Syndrome. This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2009, Biotech Business Week via NewsRx.com.
|
