RETT SYNDROME GENETICS, PATHOGENESIS & SEARCH FOR MARKER

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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. The general goal of the Rett Syndrome program project is to improve the understanding of the genetics and pathogenesis of Rett syndrome, as a first step to improved diagnosis and treatment. A significant component of this collaboration is MR neuroimaging and MR spectroscopic imaging. There are several aspects to this research for which collaboration with the resource is extremely important. First of all, a large fraction of the subjects with Rett Syndrome are children, who require a special environment to feel comfortable to participate in the scanning. Also, many adults with Rett syndrome have mental retardation and need special attention in order to be scanned successfully. The magnets in our center have the shortest bore available of all whole-body 1.5T and 3T scanners. The bore is accessible from the back and the front and allows the subject to keep eye contact with its care giver. This child-friendly environment for MR imaging is expected to drastically reduce the requir ements for sedation because the child is more at ease. The Kirby Center also contains a mock scanner in which the children or other subjects can be trained to hold still and perform tasks in the magnet. Together with the child psychologists at Kennedy Krieger, Dr. Naidu and the Center staff will work on optimizing the imaging of children. The latter is important because it is expected that functional testing of these children can provide much needed information on their behavior in a quantitative reproducible manner. The Rett Syndrome research program relates to all of the development projects proposed in this resource application. The design of flow and oxygenation methods and techniques for improved image registration and processing in Project 1 will be used to examine the hypothesis of abnormal blood flow and oxygen metabolism in the frontal lobe in Rett syndrome (see below). The spectroscopy tools in project 2 will be used to determine levels of neurotransmitters and other brain chemicals with respect to normal children. Project 3 will, for the first time, provide the possibility to compare the wiring in the brains of children with Rett syndrome to that of normal children. Projects 4 will be crucial in establishing shapes of brain regions and in combining the results of all projects in general maps that will be assessed as a function of developmental stage.