Dataset Information

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

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 In this update, we summarize a total of 83 different WRN mutations, including eight previously unpublished mutations identified by the International Registry of Werner Syndrome (Seattle, WA) and the Japanese Werner Consortium (Chiba, Japan), as well as 75 mutations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

SUBMITTER: Yokote K

PROVIDER: S-EPMC5237432 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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

Yokote Koutaro K Chanprasert Sirisak S Lee Lin L Eirich Katharina K Takemoto Minoru M Watanabe Aki A Koizumi Naoko N Lessel Davor D Mori Takayasu T Hisama Fuki M FM Ladd Paula D PD Angle Brad B Baris Hagit H Cefle Kivanc K Palanduz Sukru S Ozturk Sukru S Chateau Antoinette A Deguchi Kentaro K Easwar T K M TK Federico Antonio A Fox Amy A Grebe Theresa A TA Hay Beverly B Nampoothiri Sheela S Seiter Karen K Streeten Elizabeth E Piña-Aguilar Raul E RE Poke Gemma G Poot Martin M Posmyk Renata R Martin George M GM Kubisch Christian C Schindler Detlev D Oshima Junko J

Human mutation 20161007 1

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 ...[more]

PMID: 27667302

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Project description:IntroductionPatient registries, 'organised systems that use observational methods to collect uniform data on a population defined by a particular disease, condition, or exposure, and that is followed over time', are potentially valuable sources of data for supporting regulatory decision-making, especially for products to treat rare diseases. Nevertheless, patient registries are greatly underused in regulatory assessments. Reasons include heterogeneity in registry design and in the data collected, even across registries for the same disease, as well as unreliable data quality and data sharing impediments. The Patient Registries Initiative was established by the European Medicines Agency in 2015 to support registries in collecting data suitable to contribute to regulatory assessments, especially post-authorisation safety and effectiveness studies.MethodsWe conducted a qualitative synthesis of the published observations and recommendations from an initiative-led multi-stakeholder consultation and four disease-specific patient registry workshops. We identified the primary factors facilitating the use of registry data in regulatory assessments. We generated proposals on operational measures needed from stakeholders including registry holders, patients, healthcare professionals, regulators, marketing authorisation applicants and holders, and health technology assessment bodies for implementing these.ResultsTen factors were identified as facilitating registry use for supporting regulatory assessments of medicinal products. Proposals on operational measures needed for implementation were categorised according to three themes: (1) nature of the data collected and registry quality assurance processes; (2) registry governance, informed consent, data protection and sharing; and (3) stakeholder communication and planning of benefit-risk assessments.ConclusionsThese are the first explicit proposals, from a regulatory perspective, on operational methods for increasing the use of patient registries in medicines regulation. They apply to registry holders, patients, regulators, marketing authorisation holders/applicants and healthcare stakeholders broadly, and their implementation would greatly facilitate the use of these valuable data sources in regulatory decision-making.

Dataset Information

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

Publications

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

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