THE MOLECULAR BASIS AND CLINICAL SPECTRUM OF ROTHMUND-THOMSON SYNDROME

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 Rothmund-Thomson综合征(RTS)是一种罕见的遗传性疾病，具有多种临床特征，包括明显的癌症易感性。患有RTS的人可能只有几个或许多临床特征。RTS的诊断有时很困难，因为没有实验室检查或细胞检测可以诊断，而且临床表现可能是静止的。在一些RTS患者中发现了一种名为RecQL4的基因突变。然而，RTS突变的全谱还没有完全确定，而且还没有建立基因/表型的相关性。RecQ解旋酶家族的其他疾病包括Bloom综合征和Werner综合征，它们与RTS有相同的临床特征，包括显著的癌症风险。最近已经做了很多工作来促进对这些其他疾病所涉及的分子途径的了解，并且关于这些其他相关疾病的临床信息要多得多。相比之下，对RTS的了解要少得多，也没有关于RTS的大规模临床或分子研究的报道。由于RTS在世界范围内是一种罕见的疾病，收集受影响的患者及其亲属、积累相关的医学信息和收集生物标本成为一项艰巨的任务。这项研究将允许研究人员将患有RTS的受试者带到研究机构，以便进行全面的临床和实验室调查，并收集生物样本，然后用于分子和遗传学研究。这些研究将有助于更好地了解与RTS相关的临床问题，以及这种异质性疾病背后的遗传学缺陷。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Rothmund-Thomson Syndrome (RTS) is a rare genetic disorder with multiple clinical features including a significant cancer predisposition. Individuals with RTS may have just a few or many clinical features. Diagnosis of RTS is sometimes difficult since there is no laboratory test or cellular assay which is diagnostic, and the clinical presentation can be quiate variable. One gene, RecQL4, has been found to be mutated in some RTS patients. However, the full spectrum of mutations in RTS has not been fully characterized, and genotype/phenotype coreelations have yet to be established. Other disorders in the RecQ helicase family include Bloom Syndrome and Werner Syndrome, which share clinical features with RTS, including significant cancer risk. Much work has been done recently to advance the understanding of the molecular pathways involved in these other disorders, and much more clinical information is known about these other related disorders. In contrast, much less is known about RTS, and no large scale clinical or molecular study of RTS has been reported. Because RTS is a rare disorder worldwide, accruing affected patients and their relatives, accumulating pertinent medical information, and collecting biologic specimens become difficult tasks. This study would allow investigators to bring subjects with RTS to the study institution in order to perform comprehensive clinical and laboratory investigation and to collect biologic samples, which can then be used for molecular and genetic studies. These studies will lead to better understanding of the clinical problems associated with RTS and of the genetics defects which underlie this heterogeneous disorder.