WILLIAMS SYNDROME: BRIDGING COGNITION AND GENES

该计划项目的总体目标是在 认知、大脑和基因。威廉姆斯综合征(WMS)，一种罕见的遗传性- 基础障碍，导致精神发育迟滞，独特的相貌，和 特定的心脏缺陷。在对WMS受试者的研究中，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)巨大的认知缺陷，但 显著节省了语言；和(B)空间认知的极端障碍 但是出色的面部处理技术。此外，我们还发现，WMS的叶子 大脑上的一个独特的形态特征，表现在两个方面 神经生理学和神经解剖学发现。最近，WMS一直在 显示与弹性蛋白基因周围的半合子缺失有关 染色体上的7q11位点。这一发现允许在令人兴奋的新系列中 可能从大脑和认知后遗症之间建立联系的研究 这种罕见的疾病与其遗传基础有关，从而延长了认知能力 神经科学发展到分子遗传学的水平。在项目I中： 神经认知特征，我们将确定神经心理学 100名WMS受试者的档案，使用认知探测器 这是该综合症的明显标志。项目I还将应用一套精炼的 来表征内部解离的性质和程度 WMS配置文件。项目2：我们的神经生理学特征 将使用事件相关电位来研究WMS患者的大脑功能 研究对象。在项目III中：我们将在 活体磁共振成像检查独特的大脑结构 在WMS中。我们将用新的高分辨率技术扩大我们的研究 使我们能够解决关于大脑/行为关系的特定假设 神经系统的术语。项目4：脑细胞结构 我们将定位和检查脑细胞构筑 WMS异常包括神经元成熟异常。在项目5中： 分子遗传学特征我们将确定基因座和范围 在每个WMS受试者中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 基因作图。该计划项目由两个核心提供服务： 管理、统计和计算机服务以及诊断方法 和服务，将提供行为诊断、神经成像(ERP) 和核磁共振)、脑部尸检样本和生物样本。该计划 项目还将提供最近提供的单独服务 成立了威廉姆斯综合征诊所。通过耦合神经心理学， 本计划项目的神经解剖学和遗传学结果，我们可以 有助于更好地理解WMS，并最终帮助理解 脑结构和功能与基因的关系。

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.