Werner syndrome is a rare autosomal recessive disorder characterized by a constellation of adult onset phenotypes consistent with an acceleration of intrinsic biological aging. It is caused by pathogenic variants in the WRN gene, which encodes a multifunctional nuclear protein with exonuclease and helicase activities. WRN protein is thought to be involved in optimizations of various aspects of DNA metabolism, including DNA repair, recombination, replication and transcription. In this update, we summarize a total of 83 different WRN mutations, including 8 previously unpublished mutations identified by the International Registry of Werner Syndrome (Seattle, WA) and the Japanese Werner Consortium (Chiba, Japan), as well as 75 mutations already reported in the literature. The Seattle International Registry recruits patients from all over the world to investigate genetic causes of a wide variety of progeroid syndromes in order to contribute to the knowledge of basic mechanisms of human aging. Given the unusually high prevalence of Werner syndrome patients and heterozygous carriers in Japan, the major goal of the Japanese Consortium is to develop effective therapies and to establish management guidelines for Werner syndrome patients in Japan and elsewhere. This review will also discuss potential translational approaches to this disorder, including those currently under investigation. This article is protected by copyright. All rights reserved.
