THE CHROMOSOME 18 CLINICAL RESEARCH CENTER

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目的：无染色体综合征是由染色体区域丢失或复制引起的染色体疾病。关于血管畸形如何导致疾病，有两种截然相反的观点。一种观点强烈支持这样的观点，即染色体不平衡，无论哪个区域不平衡，都足以解释肿瘤综合征中的许多表型特征。由于大多数新生血管综合征导致广泛的特征，如智力低下，专家认为，单基因与这些表型相关的可能性很小。另一种观点认为，通过分析各种各样的综合征，可以证明不同的非整倍体表型是特定的，彼此之间是可以区分的。从这些信息可以推断，非整倍体的表型是由在不平衡区域编码的特定基因决定的。在圣安东尼奥，我们正在系统地研究患有18号染色体新染色体的儿童，以检验以下假设： 1.伴有18号染色体缺失的儿童生长激素缺乏伴有认知和脑微结构的异常，生长激素治疗可以改善这种异常。 2.18号染色体异常个体的生理和行为发现是由于非二倍体上存在的基因所致。因此，将生理和行为发现与它们的缺失程度相关联，将有助于识别涉及的基因。了解这些发现的分子机制将为设计适当的治疗方法提供必要的洞察力。 方法：UTHSCSA儿科成立18号染色体临床研究中心，目标如下： 1.成为18号染色体异常个体家庭的国际医疗和教育资源。 2.进行和促进与18号染色体综合征有关的临床和基础研究。 3.设计治疗方法，帮助这些人克服染色体异常的影响。 为了实现这些目标，必须收集关于这些个体的表型和基因的广泛数据：因此，我们提出以下具体目标： 1.执行基因分型分析以确定： A.受影响个体的基因类型 B.异常的染色体的起源亲本 2.收集18号染色体异常个体的全面临床数据，包括： A.生长激素状态的测定。 B.促肾上腺皮质激素、甲状腺和性激素水平的测定 C.行为和神经心理测评 D.听力学和耳、鼻、喉检查 E.大脑的磁共振成像(MRI) F.畸形学评价 G.神经病学检查 H.牙科评估 一、言语病理学评价 J.精神病学评估 表型评估将是纵向的；因此，参与者的年龄范围将很广。这种广泛的年龄范围，以及一些参与者可能会被多次评估的事实，意味着我们评估的每一部分可能并不适合每次访问的每一位参与者。

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.