WRN Mutation Update: Mutation Spectrum, Patient Registries, and Translational Prospects
Department of Pediatrics, Division of Genetics
Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Genetics and Genomics | Pediatrics
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 In this update, we summarize a total of 83 different WRN mutations, including eight previously unpublished mutations identified by the International Registry of Werner Syndrome (Seattle, WA) and the Japanese Werner Consortium (Chiba, Japan), as well as 75 mutations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.
Werner syndrome, Progeroid syndrome, WRN, RECQL2, RECQ3, RecQ helicase
DOI of Published Version
Hum Mutat. 2016 Sep 26. doi: 10.1002/humu.23128. Link to article on publisher's site
Yokote, Koutaro; Hay, Beverly N.; and Oshima, Junko, "WRN Mutation Update: Mutation Spectrum, Patient Registries, and Translational Prospects" (2016). Pediatric Publications and Presentations. 103.