International Registry of Werner Syndrome

维尔纳综合征国际登记处

• 批准号: 8521042
• 负责人: GEORGE M. MARTIN
• 金额: $ 18.9万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-15 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8521042
• 关键词: Adult; Affect; Aging; Alleles; Appearance; Area; Atherosclerosis; Bilateral; Biochemical Genetics; Biocompatible Materials; Biological; Biological Aging; Blood specimen; Boston; Cancer Center; Cataract; Centenarian; Clinical; Clinical Data; Code; Collaborations; Communities; Complementary DNA; Cultured Cells; DNA Damage; Development; Diagnosis; Disease; Enhancers; Epidemiologic Studies; Epithelial; Exonuclease; Eye Development; Family; Family member; Fibroblasts; Funding; General Population; Genes; Genetic; Genetic Research; Genome; Genome Stability; Genotype; Germany; Goals; Human; International; Investigation; Japan; Japanese Population; Longevity; Maintenance; Malignant Neoplasms; Medicine; Methodology; Molecular Diagnosis; Mutation; Non-Insulin-Dependent Diabetes Mellitus; Nonsense-Mediated Decay; Octogenarian; Osteoporosis; Parents; Pathway interactions; Patients; Phenotype; Plasma; Reagent; Recruitment Activity; Registries; Research; Research Institute; Research Personnel; Resistance; Resources; Sampling; Siblings; Skin; Speed; Stem cells; Structure; Surveys; Syndrome; Tissue Sample; Universities; WRN gene; Washington; Werner Syndrome; Work; age related; aged; base; biological research; college; established cell line; exome sequencing; genetic linkage analysis; genetic pedigree; helicase; human WRN protein; interest; lens; lymphoblastoid cell line; middle age; novel; null mutation; peripheral blood; senescence

Werner syndrome (WS) is the prototypic segmental progeroid syndrome. Started in 1988, the International Registry of Werner Syndrome has served as a resource to ascertain and genotype WS pedigrees, establish and cryopreserve biological materials from these pedigrees and provide these materials to investigators around the world. We also provide public information about WS to clinicians and to the general public. This network of resources led to the discovery of the WRN gene responsible for classical WS as well as novel LMNA mutations among patients with atypical Werner syndrome (AWS). As requested by the Japanese Werner Consortium (P.I. Koutaro Yokote, Chiba University, Japan), we assist in their nation-wide survey of WS and in collaborative epidemiological studies to evaluate the phenotypes of heterozygous carriers of WRN mutations (Keitaro Matsuo, Aichi Cancer Center Research Institute, Japan). The Registry has evolved to accept cases with a broader range of progeroid phenotypes in order to facilitate the discovery of new biochemical genetic pathways with the potential to modulate mechanisms of intrinsic biological aging. Examples include HapMap linkage analysis (P.I. Christian Kubisch, University of Ulm, Germany) and whole exome sequencing (P.I. Deborah Nickerson, University of Washington). We now propose to expand the scope of our Werner Registry to seek evidence for alleles at WRN and other loci that are associated with unusually enhanced functions. We will bring together two heretofore rather separate gerontologic communities: our colleagues who focus on deleterious mutations associated with progeroid syndromes and those interested in the genetic basis of unusually successful aging (Thomas Perls, Boston University, Nir Barzilai, Albert Einstein College of Medicine). The initial focus is to elucidate the functional significance of WRN SNPs in coding areas and putative cis-regulatory domains associated with exceptional longevity (Akira Yasui, Tohoku University, Japan; Lawrence A. Loeb, University of Washington). These studies will be extended to other relevant loci, including LMNA and newly identified AWS genes.

Werner综合征（WS）是典型的节段性类早衰综合征。从1988年开始，国际沃纳综合征登记处已经成为确定WS谱系和基因分型的资源，建立和冷冻保存这些谱系的生物材料，并将这些材料提供给世界各地的研究人员。我们还向临床医生和公众提供有关WS的公共信息。这一资源网络导致了WRN基因在非典型维尔纳综合征（AWS）患者中引起经典WS和新型LMNA突变的发现。应日本Werner Consortium （P.I. Koutaro Yokote，千叶大学，日本）的要求，我们协助他们进行全国范围的WS调查和合作流行病学研究，以评估WRN突变杂合携带者的表型（Keitaro Matsuo，爱知癌症中心研究所，日本）。