Is it Williams syndrome? GTF2IRD1 implicated in visual-spatial construction and GTF2I in sociability revealed by high resolution arrays

Bibliographic Collection: 
CARTA-Inspired Publication
Publication Type: Journal Article
Authors: Dai, L.; Bellugi, U.; Chen, X. N.; Pulst-Korenberg, A. M.; Jarvinen-Pasley, A.; Tirosh-Wagner, T.; Eis, P. S.; Graham, J.; Mills, D.; Searcy, Y.; Korenberg, J. R.
Year of Publication: 2009
Journal: Am J Med Genet A
Volume: 149A
Edition: 2009/02/11
Number: 3
Pagination: 302-14
Date Published: Mar
Type of Article: Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't
Publication Language: eng
ISBN Number: 1552-4833 (Electronic)15
Keywords: *Social Behavior, *Vision, Humans, Muscle Proteins/*genetics, Nuclear Proteins/*genetics, Ocular, Oligonucleotide Array Sequence Analysis/*methods, Trans-Activators/*genetics, Williams Syndrome/*genetics/*psychology

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 visual-spatial cognition and social behavior. We defined a approximately 1.5 Mb region of approximately 25 genes deleted in >98% of typical WS and then rare small deletions, showing that visual-spatial construction (VSC) in WS was associated with the genes GTF2IRD1 and GTF2I. To distinguish the roles of GTF2IRD1 and GTF2I in VSC and social behavior, we utilized multiple genomic methods (custom high resolution oligonucleotide microarray, multicolor FISH and somatic cell hybrids analyzed by PCR) to identify individuals deleted for either gene but not both. We analyzed genetic, cognitive and social behavior in a unique individual with WS features (heart defects, small size, facies), but with an atypical deletion of a set of genes that includes GTF2IRD1, but not GTF2I. The centromeric breakpoint localized to the region 72.32-72.38 Mb and the telomeric breakpoint to 72.66 Mb, 10 kb downstream of GTF2IRD1. Cognitive testing (WPPSI-R, K-BIT, and PLS-3) demonstrated striking deficits in VSC (Block Design, Object Assembly) but overall performance 1.5-3 SD above WS means. We have now integrated the genetic, clinical and cognitive data with previous reports of social behavior in this subject. These results combine with previous data from small deletions to suggest the gene GTF2IRD1 is associated with WS facies and VSC, and that GTF2I may contribute to WS social behaviors including increased gaze and attention to strangers.


Am J Med Genet A. 2009 Mar;149A(3):302-14. doi: 10.1002/ajmg.a.32652.

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Alternate Journal: American journal of medical genetics. Part A
Author Address:

The Center for Integrated Neuroscience and Human Behavior, The Brain Institute, University of Utah, Salt Lake City, Utah 84108, USA.