THE MOLECULAR BASIS AND CLINICAL SPECTRUM OF ROTHMUND-THOMSON SYNDROME

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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.