THE CHROMOSOME 18 CLINICAL RESEARCH CENTER

18 号染色体临床研究中心

• 批准号: 7718732
• 负责人: JANNINE De Mars CODY
• 金额: $ 0.1万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7718732
• 关键词: Affect; Age; Aneuploidy; Basic Science; Behavioral; Brain; Child; Chromosomal Duplication; Chromosome abnormality; Chromosomes; Chromosomes, Human, Pair 18; Clinical; Clinical Data; Clinical Research; Cognitive; Computer Retrieval of Information on Scientific Projects Database; Congenital chromosomal disease; Corticotropin; Data; Dental; Diploidy; Disease; Dysmorphology; Ear; Evaluation; Family; Funding; Genes; Genotype; Goals; Gonadal Steroid Hormones; Grant; Individual; Institution; International; Magnetic Resonance Imaging; Measurement; Medical; Mental Retardation; Molecular; Neurology; Nose; Numbers; Parents; Participant; Pharyngeal structure; Phenotype; Range; Research; Research Personnel; Resources; Somatotropin; Source; Speech Pathology; Syndrome; Testing; Thyroid Gland; Time; United States National Institutes of Health; Visit; growth hormone deficiency; insight; pediatric department

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 目的：动脉法综合症是染色体区域丧失或重复的染色体疾病。 关于动脉症如何引起疾病，有两种相反的看法。 一种观点强烈支持这样一个观念，即无论哪个区域不平衡，染色体失衡都足以解释动脉苏综合征中看到的许多表型特征。 由于大多数动脉切开术综合征都带来了诸如智力低下的广泛特征，因此专家认为，与这些表型的单基因相关性很大。 另一种观点认为，通过分析多种综合征，可以证明不同的非整倍体表型是特定的，并且可以彼此区分。 从这些信息可以推断出非整倍体表型取决于在不平衡区域中编码的特定基因。 在圣安东尼奥（San Antonio），我们正在系统地研究染色体18个障碍物的儿童，以检验以下假设： 1。染色体18缺失儿童的生长激素缺乏症伴随着大脑的认知和微观结构异常，可以通过GH疗法改善。 2。18染色体异常的个体的身体和行为发现是由于存在于非二倍数字上的基因所致。因此，物理和行为发现与其缺失程度的相关性将有助于识别所涉及的基因。对这些发现的分子机制的理解将为设计适当的治疗所需的见解提供。 方法：UTHSCSA儿科部建立了18号染色体临床研究中心，其目标以下三个目标： 1。成为针对18个异常染色体患者家庭的国际医学和教育资源。 2。执行并促进与染色体第18个综合征有关的临床和基础研究。 3。设计治疗以帮助这些人克服其染色体异常的影响。 为了实现这些目标，必须在这些个体的表型和基因型上收集大量数据：因此，我们提出以下特定目的： 1。执行基因型分析以确定： 答：受影响个体的基因型 B.异常的染色体起源父母 2。收集有关染色体18个异常患者的综合临床数据，包括： A.确定生长激素状况。 B.皮质运动，甲状腺和性激素水平的测量 C.行为和神经心理测量评估 D.听力学和耳朵，鼻子和喉咙检查 E.大脑的磁共振成像（MRI） F.畸形评估 G.神经病学检查 H.牙科评估 I.语音病理评估 J.精神病评估 表型评估将是纵向的；因此，参与者的年龄范围很广。这个广泛的年龄范围以及某些参与者可以多次评估的事实意味着我们评估的每个组成部分可能并不适合每次访问时的每个参与者。