WILLIAMS SYNDROME: BRIDGING COGNITION AND GENES

该项目的总体目标是在以下方面建立桥梁： 认知、大脑和基因。 威廉姆斯综合征（WMS），一种罕见的遗传- 基础障碍，导致智力迟钝，独特的面容，和 特殊的心脏缺陷 在对WMS主题的研究中，我们发现， 综合征也可能导致认知功能的特异性分离， 在领域内和跨领域：（a）巨大的认知缺陷， 明显的语言;（B）空间认知的极端障碍 但面部处理能力很强 此外，我们还发现， 大脑上独特的形态印记，表现在两个 神经生理学和神经解剖学发现。 最近，WMS已经 显示与弹性蛋白基因周围的半合子缺失有关 在染色体上，7 q11位点。 这一发现允许令人兴奋的新系列 研究可能会从大脑和认知后遗症中建立联系， 这种罕见的疾病，其遗传基础，从而扩大认知 神经科学到分子遗传学的水平。 在项目I中： 神经认知表征，我们将确定神经心理学 100名WMS受试者的个人资料，使用认知探针， 症状的明显标志物。 项目I还将应用一组改进的 的性质和程度的解离内 WMS profile。 在项目2：神经生理学表征中， 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 活体磁共振成像检查独特的大脑结构 在WMS。 我们将用新的高分辨率技术扩大我们的研究 使我们能够解决大脑/行为关系的特定假设， 神经系统的术语 项目4：脑细胞结构 我们将定位并检查大脑细胞结构 WMS异常，包括异常神经元成熟。 项目5： 分子遗传学表征我们将确定基因座和程度 在每个WMS受试者中， 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服务： 行政、统计和计算机服务及诊断方法 和服务，将提供行为诊断，神经成像（ERP 和MRI）、脑尸检样品和生物样品。 程序 项目还将提供最近的单独服务， 建立了威廉姆斯综合症诊所。 通过结合神经心理学， 神经解剖学和遗传学的结果，我们可以 有助于更好地理解WMS，并最终 大脑结构和功能与基因之间的关系。

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.