Molecular Basis and Clinical Spectrum of Rothmund-Thomson Syndrome
The aim of our study is to characterize the clinical and molecular features of Rothmund-Thomson syndrome (RTS), a rare genetic developmental disorder with heterogeneous clinical findings, including growth and developmental delay, skin, bone and dental abnormalities, juvenile cataracts, skin rash, and increased predisposition to bone cancer (osteosarcoma).
We have completed clinical evaluation on 28 Rothmund-Thomson syndrome patients in the General Clinical Research Center at Texas Children's Hospital and have collected clinical, cytogenetic and skeletal survey results on these patients as well as mutation analysis of their RECQL4 genes.The skeletal findings included many skeletal abnormalities not previously described in these patients and did not include several findings that have been previously described.
One of the other major findings from examining the skeletal surveys of RTS patients is that a significant proportion has osteopenia on radiographs. We are now examining their bones in more detail by obtaining DXA scans for bone mineral density as well as laboratory studies for bone turnover. We are also collaborating with Dr. Brendan Lee in the Department of Human and Molecular Genetics at BCM to make a conditional mutant mouse where the RECQL4 gene is knocked out specifically in the bone. This will allow us to examine in more detail the skeletal defects in these patients. The support of the IDDRC in our continuing research of this rare genetic developmental disorder is invaluable.
Relevance of the project to IDDRC mission:
RTS is a developmental disorder that manifests in early infancy. Patients suffer many disabilities, and have delays in both physical and mental development. Our goals are to understand the full clinical spectrum of this rare genetic disorder and to try to improve the quality of life of affected individuals and their disability whenever possible.