Human Genetics

, Volume 124, Issue 4, pp 369–377 | Cite as

The clinical characteristics of Werner syndrome: molecular and biochemical diagnosis

  • Meltem Muftuoglu
  • Junko Oshima
  • Cayetano von Kobbe
  • Wen-Hsing Cheng
  • Dru F. Leistritz
  • Vilhelm A. BohrEmail author
Review Article


Werner syndrome (WS) is an adult onset segmental progeroid syndrome caused by mutations in the WRN gene. The WRN gene encodes a 180 kDa nuclear protein that possesses helicase and exonuclease activities. The absence of WRN protein leads to abnormalities in various DNA metabolic pathways such as DNA repair, replication and telomere maintenance. Individuals with WS generally develop normally until the third decade of life, when premature aging phenotypes and a series of age-related disorders begin to manifest. In Japan, where a founder effect has been described, the frequency of Werner heterozygotes appears to be as high as 1/180 in the general population. Due to the relatively non-specific nature of the symptoms and the lack of awareness of the condition, this disease may be under-diagnosed in other parts of the world. Genetic counseling of WS patients follows the path of other autosomal recessive disorders, with special attention needed for cancer surveillance in relatives. Molecular diagnosis of WS is made by nucleotide sequencing and, in some cases, protein analysis. It is also of potential interest to measure WRN activities in WS patients. More than 50 different disease-causing mutations in the WRN gene have been identified in WS patients from all over the world. All but one of these cases has mutations that result in the premature termination of the protein. Here we describe the clinical, molecular and biochemical characteristics of WS for use by medical professionals in a health care setting. Additional information is available through the International Registry of WS (


Exonuclease Activity Werner Syndrome LMNA Gene LMNA Mutation Progeroid Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was partially supported by the Intramural Research Program of the NIH, National Institute on Aging, and by the NIH grant CA78088 (to J.O).


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Copyright information

© U. S. Government 2008

Authors and Affiliations

  • Meltem Muftuoglu
    • 1
  • Junko Oshima
    • 2
  • Cayetano von Kobbe
    • 3
  • Wen-Hsing Cheng
    • 4
  • Dru F. Leistritz
    • 2
  • Vilhelm A. Bohr
    • 1
    Email author
  1. 1.Laboratory of Molecular GerontologyNational Institute on Aging, NIHBaltimoreUSA
  2. 2.Department of PathologyUniversity of WashingtonSeattleUSA
  3. 3.Cancer Vaccines GroupChimera Pharma (Bionostra Group)MadridSpain
  4. 4.Department of Nutrition and Food ScienceUniversity of MarylandCollege ParkUSA

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