WRN Mutation Update: Mutation Spectrum, Patient Registries, and Translational Prospects

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 FedericoAmy Fox, Theresa A. Grebe, Beverly Hay, Sheela Nampoothiri, Karen Seiter, Elizabeth Streeten, Raul Eduardo Pina Aguilar, Gemma Poke, Martin Poot, Renata Posmyk, George M. Martin, Christian Kubisch, Detlev Schindler, Junko Oshima*

*Corresponding author for this work

Research output: Contribution to journalArticle

36 Citations (Scopus)

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 In this update, we summarize a total of 83 different WRN mutations, including eight previously unpublished mutations identified by the International Registry of Werner Syndrome (Seattle, WA) and the Japanese Werner Consortium (Chiba, Japan), as well as 75 mutations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.

Original languageEnglish
Pages (from-to)7-15
Number of pages9
JournalHuman Mutation
Volume38
Issue number1
Early online date7 Oct 2016
DOIs
Publication statusPublished - Jan 2017

Keywords

  • Progeroid syndrome
  • RecQ helicase
  • RECQ3
  • RECQL2
  • Werner syndrome
  • WRN

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    Yokote, K., Chanprasert, S., Lee, L., Eirich, K., Takemoto, M., Watanabe, A., Koizumi, N., Lessel, D., Mori, T., Hisama, F. M., Ladd, P. D., Angle, B., Baris, H., Cefle, K., Palanduz, S., Ozturk, S., Chateau, A., Deguchi, K., Easwar, T. K. M., ... Oshima, J. (2017). WRN Mutation Update: Mutation Spectrum, Patient Registries, and Translational Prospects. Human Mutation, 38(1), 7-15. https://doi.org/10.1002/humu.23128