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

Autor: Yokote K; Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan., Chanprasert S; Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington., Lee L; Department of Pathology, University of Washington, Seattle, Washington., Eirich K; Department of Human Genetics, University of Wuerzburg, Wuerzburg, Germany., Takemoto M; Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan., Watanabe A; Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan., Koizumi N; Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan., Lessel D; Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Mori T; Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, Washington., Hisama FM; Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington., Ladd PD; Department of Pathology, University of Washington, Seattle, Washington., Angle B; Advocate Lutheran General Hospital and Advocate Children's Hospital, Park Ridge, Illinois., Baris H; The Genetics Institute, Rambam Health Care Campus and Rappaport School of Medicine, Technion - Israel Institute of Technology, Haifa, Israel., Cefle K; Department of Internal Medicine, Division of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Turkey., Palanduz S; Department of Internal Medicine, Division of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Turkey., Ozturk S; Department of Internal Medicine, Division of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Turkey., Chateau A; Department of Dermatology, Greys Hospital, Pietermaritzburg, South Africa., Deguchi K; Department of Neurology, Okayama City Hospital, Okayama, Japan., Easwar TK; Milestone Hospital, Rajkot, India., Federico A; Department of Medicine, Surgery and Neurosciences, Unit Clinical Neurology and Neurometabolic Diseases, Medical School, University of Siena, Siena, Italy., Fox A; Department of Dermatology, University of North Carolina, Chapel Hill, North Carolina., Grebe TA; Division of Genetics and Metabolism, Phoenix Children's Hospital, Phoenix, Arizona., Hay B; Division of Genetics, UMass Memorial Medical Center, Worcester, Massachusetts., Nampoothiri S; Department of Pediatric Genetics, Amrita Institute of Medical Sciences and Research Center, Kochi, Kerala, India., Seiter K; Department of Medicine, New York Medical College, Hawthorne, New York., Streeten E; Division of Genetics, University of Maryland School of Medicine, Baltimore, Maryland., Piña-Aguilar RE; Centro Médico Nacional 20 de Noviembre, ISSSTE, Mexico City, Mexico., Poke G; Genetic Health Service NZ, Wellington, New Zealand., Poot M; University Medical Center, Utrecht, Netherlands., Posmyk R; Department of Clinical Genetics, Podlaskie Medical Center, Bialystok, Poland.; Department of Perinatology, Medical University of Bialystok, Bialystok, Poland., Martin GM; Department of Pathology, University of Washington, Seattle, Washington., Kubisch C; Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Schindler D; Department of Human Genetics, University of Wuerzburg, Wuerzburg, Germany., Oshima J; Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.; Department of Pathology, University of Washington, Seattle, Washington.
Jazyk: angličtina
Zdroj: Human mutation [Hum Mutat] 2017 Jan; Vol. 38 (1), pp. 7-15. Date of Electronic Publication: 2016 Oct 07.
DOI: 10.1002/humu.23128
Abstrakt: 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.
(© 2016 WILEY PERIODICALS, INC.)
Databáze: MEDLINE
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