WILLIAMS SYNDROME: BRIDGING COGNITION AND GENES

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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.