Event Abstract

Is it Williams Syndrome? GTF2I Implicated in Sociability and GTF2IRD1 in Visual-Spatial Construction Revealed by High Resolution Arrays

  • 1 Cedars-Sinai Medical Center at UCLA, Departments of Pediatrics and Medical Genetics Institute, USA
  • 2 The Salk Institute for Biological Studies, Laboratory for Cognitive Neuroscience, USA
  • 3 Stanford University, School of Medicine, USA
  • 4 University of Zagreb, Department of Psychology, USA

Genetic contributions to human cognition and behavior are clear but difficult to define. Williams syndrome (WS) provides a unique model for relating single genes to visualspatial cognition and social behavior. We defined a ~1.5 Mb region of ~25 genes deleted in >98% of typical WS and then small deletions in rare cases, showing that visualspatial construction (VSC) in WS was associated with the genes GTF2IRD1 and GTF2I 1. To distinguish the roles of GTF2IRD1 and GTF2I in VSC and social behavior, we developed multiple genomic reagents (a custom high resolution oligonucleotide array spanning 14Mb of the WS and flanking duplicated regions, multicolor FISH and somatic cell hybrids analyzed by PCR) to identify individuals deleted for either gene but not both. We analyzed genetic, expression, cognitive and social behavior in atypical and typical deletion WS. The results indicate a rare individual with WS features (heart disease, small size, facies), but atypical deletion of all genes from FKBP6 through GTF2IRD1, but not GTF2I. At sub-exon resolution, the centromeric breakpoint localized to 72.38 Mb within intron 2 of the gene FKBP6 and the telomeric to 72.66 Mb, 10 kb downstream of the gene for GTF2IRD1. Cognitive testing (WPPSI-R, KBIT, and PLS-3) revealed striking deficits in VSC (Block Design, Object Assembly) but overall performance 1.5-3 SD above WS means. Social behavior, evaluated quantitatively, revealed decreased global sociability and approach to strangers, less eye contact and more involvement in non-social activities than typical WS. These results define WS breakpoints, indicate the gene GTF2IRD1 is responsible for a large part of typical WS facies and VSC, and that GTF2I contributes to WS social behaviors including increased gaze and attention to strangers.

Conference: 12th International Professional Conference on Williams Syndrome, Garden Grove,CA, USA, 13 Jul - 14 Jul, 2008.

Presentation Type: Poster Presentation

Topic: Multidisciplinary Poster Session

Citation: Dai L, Bellugi U, Chen XN, Pulst- Korenberg AM, Järvinen-Pasley A, Wagner TT, Eis PS, Reiss AL, Mills DL, Simon A, Searcy Y and Korenberg JR (2009). Is it Williams Syndrome? GTF2I Implicated in Sociability and GTF2IRD1 in Visual-Spatial Construction Revealed by High Resolution Arrays. Front. Hum. Neurosci. Conference Abstract: 12th International Professional Conference on Williams Syndrome. doi: 10.3389/conf.neuro.09.2009.07.046

Received: 04 May 2009; Published Online: 04 May 2009.

* Correspondence: L. Dai, Cedars-Sinai Medical Center at UCLA, Departments of Pediatrics and Medical Genetics Institute, Los Angeles, USA, li.dai@cshs.org

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