WILLIAMS SYNDROME: BRIDGING COGNITION AND GENES

威廉姆斯综合症：认知和基因之间的桥梁

• 批准号: 2883142
• 负责人: URSULA BELLUGI
• 金额: $ 91.98万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-03-05 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2883142
• 关键词: Williams syndrome; adolescence (12-20); clinical research; cognition; genetic mapping; human subject; molecular genetics; molecular pathology; neurosciences

The overall aim of this Program Project is to build bridges between cognition, brain and gene. Williams syndrome (WMS), a rare genetically- based disorder, results in mental retardation, distinctive facies, and a specific heart defect. In studies of WMS subjects, we have found that the syndrome may also result in specific dissociations in cognitive function, both within and across domains: (a) massive cognitive deficits but remarkably spared language; and (b) extreme disorders in spatial cognition but excellent facial processing. Moreover, we have found that WMS leaves a distinctive morphological stamp on the brain, manifested in both neurophysiological and neuroanatomical findings. Recently, WMS has been shown to be associated with a hemizygous deletion around the elastin gene on chromosomal, locus 7q11. This finding permits on exciting new line of research that may create links from the brain and cognitive sequellae of this rare disorder to its genetic basis, thus extending cognitive neuroscience to the level of molecular genetics. In Project I: Neurocognitive Characterization, we will determine the neuropsychological profiles of 100 WMS subjects, using cognitive probes that illuminate apparent markers for the syndrome. Project I will also apply a refined set of probes to characterize the nature and extent of the dissociations within the WMS profile. In Project 2: Neurophysiological Characterization we will use event related potentials to study brain functioning in WMS subjects. In Project III: Neuroanatomic Characterization we will use in vivo magnetic resonance imaging to examine the distinctive brain structure in WMS. We will expand our studies with new high-resolution techniques allowing us to address specific hypotheses on brain/behavior relations in terms of neural systems. In Project 4: Brain Cytoarchitectonic Characterization we will locate and examine brain cytoarchitectonic anomalies in WMS including abnormal neuronal maturation. In Project 5: Molecular Genetic Characterization we will determine the locus and extent of deletion in the region surrounding the elastin gene in each WMS subject in our study, and the locations of candidate genes for the phenotype to genotype mapping. The Program Project is served by two cores: Administrative, Statistical, and Computer Services, and Diagnostic Methods and Services, which will provide Behavioral Diagnostics, Neuroimaging (ERP and MRI), Brain Autopsy samples, and Biological samples. The Program Project will also have available the separate services of the recently established Williams Syndrome Clinic. By coupling the neuropsychological, neuroanatomical, and genetic results of this Program Project, we can contribute to a greater understanding of WMS and, ultimately, of the relationship between, brain structure and function, and the gene.

该计划项目的总体目标是在 认知、大脑和基因。 威廉姆斯综合症（WMS），一种罕见的遗传性 基于疾病，导致智力低下、独特的相貌和 特定的心脏缺陷。 在 WMS 科目的研究中，我们发现 综合症还可能导致认知功能的特定分离， 在领域内和跨领域：（a）严重的认知缺陷，但是 语言非常简洁； (b) 空间认知的极端障碍 但面部处理出色。 此外，我们发现WMS离开 大脑上独特的形态印记，体现在 神经生理学和神经解剖学发现。 近期，WMS 显示与弹性蛋白基因周围的半合子缺失有关 位于染色体上，基因座 7q11。 这一发现允许令人兴奋的新系列 可能会在大脑和认知后遗症之间建立联系的研究 这种罕见的疾病有其遗传基础，从而扩展了认知能力 神经科学上升到分子遗传学水平。 在项目一中： 神经认知表征，我们将确定神经心理学 使用认知探针阐明 100 名 WMS 受试者的概况 该综合征的明显标志物。 项目我也会应用一套精致的 探针来表征内部解离的性质和程度 WMS 配置文件。 在项目 2：神经生理学表征中，我们 将使用事件相关电位来研究 WMS 中的大脑功能 科目。 在项目 III：神经解剖学表征中，我们将使用 体内磁共振成像检查独特的大脑结构 在仓库管理系统中。 我们将利用新的高分辨率技术扩展我们的研究 使我们能够解决有关大脑/行为关系的特定假设 神经系统术语。 项目 4：脑细胞结构 我们将定位并检查脑细胞结构的表征 WMS 异常，包括神经元成熟异常。 在项目5中： 分子遗传表征我们将确定基因座和范围 每个 WMS 受试者弹性蛋白基因周围区域的缺失 在我们的研究中，以及表型的候选基因的位置 基因型作图。 该计划项目由两个核心提供服务： 行政、统计和计算机服务以及诊断方法 和服务，将提供行为诊断、神经影像（ERP 和 MRI）、脑尸检样本和生物样本。 该计划 项目还将提供最近的单独服务 成立威廉姆斯综合症诊所。 通过耦合神经心理学， 该计划项目的神经解剖学和遗传学结果，我们可以 有助于更好地了解 WMS，并最终了解 大脑结构和功能与基因之间的关系。