Oshima Junko, Hisama Fuki M
Department of Pathology, University of Washington, Seattle, Wash., USA.
Gerontology. 2014;60(3):239-46. doi: 10.1159/000356030. Epub 2014 Jan 3.
Segmental progeroid syndromes are a group of disorders with multiple features resembling accelerated aging. Adult-onset Werner syndrome (WS) and childhood-onset Hutchinson-Gilford progeria syndrome are the best known examples. The discovery of genes responsible for such syndromes has facilitated our understanding of the basic mechanisms of aging as well as the pathogenesis of other common, age-related diseases. Our International Registry of Werner Syndrome accesses progeroid pedigrees from all over the world, including those for whom we have ruled out a mutation at the WRN locus. Cases without WRN mutations are operationally categorized as 'atypical WS' (AWS). In 2003, we identified LMNA mutations among a subset of AWS cases using a candidate gene approach. As of 2013, the Registry has 142 WS patients with WRN mutations, 11 AWS patients with LMNA mutations, and 49 AWS patients that have neither WRN nor LMNA mutations. Efforts are underway to identify the responsible genes for AWS with unknown genetic causes. While WS and AWS are rare disorders, the causative genes have been shown to have much wider implications for cancer, cardiovascular disease and the biology of aging. Remarkably, centenarian studies revealed WRN and LMNA polymorphic variants among those who have escaped various geriatric disorders.
节段性早老综合征是一组具有多种类似加速衰老特征的疾病。成人发病的沃纳综合征（WS）和儿童期发病的哈钦森-吉尔福德早衰综合征是最著名的例子。导致此类综合征的基因的发现促进了我们对衰老基本机制以及其他常见的、与年龄相关疾病发病机制的理解。我们的国际沃纳综合征登记处收集了来自世界各地的早衰谱系，包括那些我们已排除WRN基因座突变的谱系。没有WRN突变的病例在操作上被归类为“非典型WS”（AWS）。2003年，我们使用候选基因方法在一部分AWS病例中鉴定出LMNA突变。截至2013年，登记处有142名患有WRN突变的WS患者、11名患有LMNA突变的AWS患者以及49名既没有WRN突变也没有LMNA突变的AWS患者。正在努力确定具有未知遗传原因的AWS的致病基因。虽然WS和AWS是罕见疾病，但已证明致病基因对癌症、心血管疾病和衰老生物学具有更广泛的影响。值得注意的是，百岁老人研究在那些未患各种老年疾病的人群中发现了WRN和LMNA多态性变体。
