Year: 2016
Type: review
Abstract: Werner syndrome (WS) 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 optimization 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 In this update, we summarize a total of 83 different WRN mutations, including eight previously unpublished mutations identified by the International Registry of Werner Syndrome (Seattle, WA) and the Japanese Werner Consortium (Chiba, Japan), as well as 75 mutations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 WS patients and heterozygous carriers in Japan, the major goal of the Japanese Consortium is to develop effective therapies and to establish management guidelines for WS patients in Japan and elsewhere. This review will also discuss potential translational approaches to this disorder, including those currently under investigation.
Source: Human Mutation
DOI: 10.1002/humu.23128
Authors: Koutaro Yokote, Sirisak Chanprasert, Lin Lee, Katharina Eirich, Minoru Takemoto, Aki Watanabe, Naoko Koizumi, Davor Lessel, Takayasu Mori, Fuki M. Hisama, Paula D. Ladd, Brad Angle, Hagit Baris, Kivanc Cefle, Sukru Palanduz, Sukru Ozturk, Antoinette Chateau, Kentaro Deguchi, T.K.M Easwar, Antonio Federico, Amy Fox, Theresa A. Grebe, Beverly Hay, Sheela Nampoothiri, Karen Seiter, Elizabeth Streeten, Raul E. Piña-Aguilar, Gemma Poke, Martin Poot, Renata Posmyk, George M. Martin, Christian Kubisch, Detlev Schindler, Junko Oshima
Institutions: Chiba University, University of Washington, University of Würzburg, University Medical Center Hamburg-Eppendorf, Advocate Lutheran General Hospital, Advocate Children's Hospital, Advocate Children's Hospital, Technion – Israel Institute of Technology, Rambam Health Care Campus, Istanbul University, Grey's Hospital, Okayama City Hospital, University of Siena, University of North Carolina at Chapel Hill, Phoenix Children's Hospital, UMass Memorial Medical Center, Amrita Institute of Medical Sciences and Research Centre, New York Medical College, University of Maryland, Baltimore, Institute for Social Security and Services for State Workers, University Medical Center Utrecht, Medical University of Białystok
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Awards: Pathological elucidation of age-related diseases by integrative analyses of senescence genes, Functional analysis of R3h domain containing-like, a novel skeletal satellite-cell-expressed gene, for investigating new treatment strategy of sarcopenia, International Registry of Werner Syndrome, G5748884844, International Registry for Werner Syndrome
OpenAlex ID: W2463711363