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Werner syndrome (WS) is a premature aging disease. Estimated prevalence ranges from 0.3 to 1 in 150 000. The syndrome is rare in Europe, but is more frequently observed in regions where consanguinity remains high such as Sardinia and the North of Japan. From a clinical point of view, it is manifested by the mimicry of age-related phenotypes such as premature thinning, greying, and loss of hair, cataracts, atherosclerosis, arteriosclerosis, osteoporosis and soft tissue calcification, as well as a high incidence of some types of cancer. Bilateral ocular cataract is the most constant sign. Patients have a beaked nose, short stature, slender limbs, and stocky trunk. Typical WS is autosomal recessive, but some atypical autosomal dominant forms of WS have also been reported. In 90% of studied cases, the mutation involved is in the WRN gene (also called RECQL2 or REQ3) located on chromosome 8p12-p11.2 and responsible for complete dysfunction of the WRN protein. About 50 different mutations have been found in WS patients. The WRN protein is a member of the RecQ family of DNA helicases that are widely conserved between species and are believed to play central roles in genomic stability. The WRN protein has been shown to physically and functionally interact with a variety of DNA-processing proteins. The prognosis for WS depends on that for the diseases normally affecting the elderly: atheromatosis with cardiovascular and neurological complications, insulin-resistant diabetes and mesenchymal cancers. Treatments are so far limited to treatment of the various diseases implied in the syndrome. |