International Registry of Werner Syndrome

Werner综合征（WS）是典型的节段性早老样综合征。从1988年开始，Werner综合征国际登记处已成为确定WS谱系和基因型的资源，建立和冷冻保存来自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在非典型Werner综合征（AWS）患者中发现负责经典WS以及新型LMNA突变的WRN基因。根据日本沃纳财团（P.I. Koutaro Yokote，千叶大学，日本），我们协助他们在全国范围内的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）。 该登记处已经发展到接受更广泛的早衰表型的情况下，以促进新的生化遗传途径的发现，有可能调节内在的生物衰老机制。例子包括HapMap连锁分析（PI Christian Kubisch，乌尔姆大学，德国）和全外显子组测序（P.I. Deborah Nickerson，华盛顿大学）。我们现在建议扩大我们的维尔纳注册表的范围，以寻找WRN和其他基因座上与异常增强功能相关的等位基因的证据。 我们将把两个迄今为止相当独立的老年学团体聚集在一起：我们的同事专注于与早老综合征相关的有害突变，以及那些对异常成功衰老的遗传基础感兴趣的人（托马斯·珀尔斯，波士顿大学，尼尔·巴兹莱，阿尔伯特·爱因斯坦医学院）。最初的重点是阐明WRN SNP在编码区和推定的与异常长寿相关的顺式调节结构域中的功能意义（Akira Yasui，日本东北大学; Lawrence A. Loeb，华盛顿大学）。这些研究将扩展到其他相关基因座，包括LMNA和新发现的AWS基因。

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.