THE CHROMOSOME 18 CLINICAL RESEARCH CENTER

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。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号染色体缺失的儿童，以检验以下假设：1.18号染色体缺失儿童的生长激素缺乏伴随着大脑的认知和微结构异常，这些异常可以通过生长激素治疗来改善。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儿科建立18号染色体临床研究中心的目标如下：1.成为18号染色体异常个体家庭的国际医学和教育资源。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，帮助这些人克服其染色体异常的影响。为了实现这些目标，必须收集关于这些个体的表型和基因型的大量数据：因此，我们提出了以下具体目标：1.进行基因分型分析以确定：a.受影响个体的基因型b.异常染色体起源的亲本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量C.行为和神经心理评估D.听力和耳朵、鼻子和喉咙检查E.脑的磁共振成像F.畸形评估G.神经学检查H.牙科评估I.言语病理学评估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.