THE CHROMOSOME 18 CLINICAL RESEARCH CENTER

点击翻译按钮获取中文摘要

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. OBJECTIVE: Aneusomy syndromes are chromosomal disorders resulting from loss or duplications of chromosomal regions. There are two opposing views about how aneusomy causes disease. One view strongly supports the notion that a chromosomal imbalance, regardless of which region is unbalanced, is sufficient to explain many of the phenotypic features seen in aneusomy syndromes. Since the majority of aneusomy syndromes result in broad features such as mental retardation, experts argue that single gene correlations with these phenotypes is highly unlikely. The other view argues that by analyzing a wide variety of syndromes, it can be demonstrated that different aneuploid phenotypes are specific and distinguishable from one another. From this information it has been inferred that aneuploid phenotypes are determined by specific genes encoded in the region of imbalance. In San Antonio, we are systematically studying children with chromosome 18 aneusomies to test the following hypotheses: 1. Growth hormone deficiency in children with chromosome 18 deletions is accompanied by cognitive and microstructural abnormalities of the brain that can be ameliorated by GH therapy. 2. The physical and behavioral findings in individuals with the abnormalities of chromosome 18 are due to the genes that are present on a non-diploid number. Therefore, correlation of the physical and behavioral findings with the extent of their deletion will help to identify the genes involved. An understanding of the molecular mechanisms of these findings will provide the insight necessary to devise appropriate therapy. METHODS: The UTHSCSA Department of Pediatrics established the Chromosome 18 Clinical Research Center with the following three goals: 1. To be the international medical and educational resource for the families of individuals with chromosome 18 abnormalities. 2. To perform and facilitate both clinical and basic research relating to the syndromes of chromosome 18. 3. To devise treatments to help these individuals overcome the effects of their chromosome abnormality. In order to attain these goals, extensive data must to be gathered on both the phenotype and genotype of these individuals: We therefore propose the following specific aims: 1. Perform a genotypic analysis to determine: A. The genotype of the affected individual B. The parent of origin of the chromosome with the abnormality 2. Gather comprehensive clinical data on individuals with chromosome 18 abnormalities including: A. Determination of growth hormone status. B. Measurement of corticotropin, thyroid and sex hormone levels C. Behavioral and neuropsychometric evaluations D. Audiological and ear, nose and throat examination E. Magnetic resonance imaging (MRI) of the brain F. Dysmorphology evaluation G. Neurology examination H. Dental evaluation I. Speech Pathology evaluation J. Psychiatric evaluation The phenotypic assessment will be longitudinal; therefore the participants will have a wide age range. This wide age range as well as the fact that some participants may be assessed multiple times means that every component of our assessment may not be appropriate for every participant at every visit.