Rare disease CRC for new therapies and new diagnostics

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DESCRIPTION (provided by applicant): This is an application from an inter-institutional group of investigators with long-standing interest in Rett syndrome, Angelman syndrome (AS), and Prader-Willi syndrome (PWS) to establish a Rare Diseases Clinical Research Center (RDCRC) that would be part of the proposed Rare Diseases Clinical Research Network (RDCRN). The Center will focus on these three disorders with the expectation that they may have near-term potential for meaningful therapy. The specific aims for Rett will be to establish a phenotype/genotype correlation over a broad spectrum of Rett phenotypes, to perform longitudinal studies on a broad sample of individuals with Rett, and to perform a survival study on a broad spectrum of Rett individuals. Clinical trials may be developed based on results of studies of animal models. The specific aims for AS are to conduct a longitudinal assessment of patients with AS according to genotype, to complete the ongoing double-blind, placebo controlled trial of folic acid and betaine in AS, and to develop a follow-on clinical trial for activation of the paternal allele for UBE3A in AS patients. The specific aims for PWS are to conduct longitudinal studies according to genotype, to develop parameters and tools for clinical trials, to test whether autistic features are more frequent in UPD than in deletion cases, and other ideas from collaborators. The aim of a pilot project using comparative genomic hybridization (CGH) on microarrays would be to develop a cytogenetic test that would detect all sizable deletions and duplications of clinical relevance on a single analysis using CGH microarrays. This new methodology would also have the potential to identify new deletion and duplication syndromes. The RDCRC will utilize GCRCs in Houston, Boston, San Diego, Gainesville, and other locations. The Center is expected to function synergistically with the Mental Retardation Research Center (MRRC) at Baylor. An extensive program is proposed for training new investigators in clinical research on rare diseases. The Center will have active affiliation with the International Rett Syndrome Association (IRSA), the Angelman Syndrome Foundation (ASF), and the Prader-Willi Syndrome Association (PWSA). A website for this RDCRC is available at www.imgen.bcm.tmc.edu/rdcm, and this site will be expanded to include a wide range of information for Rett, PWS, and AS. It is anticipated that the RDCRC will expand to include other geographic sites for the three diseases to be studied initially, and it is expected that the Center can also expand to include other disorders, such as inborn errors of metabolism amenable to hepatocyte gene therapy, disorders treatable by enzyme replacement therapy, CHARGE association, incontinentia pigmenti, Smith-Magenis syndrome, Xp deletion syndromes, and other chromosomal deletion and duplication syndromes.