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PMID: 19205026 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

American journal of medical genetics. Part A ·Vol. 149A ·No. 3 ·2009-03-00 ·Pages 302-14

Dai L, Bellugi U, Chen XN, Pulst-Korenberg AM, Järvinen-Pasley A, Tirosh-Wagner T, Eis PS, Graham J, Mills D, Searcy Y, Korenberg JR

Abstract

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.

MeSH Terms
Humans Muscle Proteins/genetics Nuclear Proteins/genetics Oligonucleotide Array Sequence Analysis/methods Social Behavior Trans-Activators/genetics Vision, Ocular Williams Syndrome/genetics,psychology
Chemicals
GTF2IRD1 protein, human Muscle Proteins Nuclear Proteins Trans-Activators
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Dai L
The Center for Integrated Neuroscience and Human Behavior, The Brain Institute, University of Utah, Salt Lake City, Utah 84108, USA.
Bellugi U
Chen X-N
Pulst-Korenberg A M
Järvinen-Pasley A
Tirosh-Wagner T
Eis P S
Graham J
Mills D
Searcy Y
Korenberg J R
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Article Info
Journal
American journal of medical genetics. Part A
Abbr.
Am J Med Genet A
ISSN
1552-4833
DOI
10.1002/ajmg.a.32652
Published
2009-03-00
Pages
302-14
Language
English
Region
United States
NLM ID
101235741
PMCID
PMC2650741
Subset
IM
Grants
NICHD NIH HHS · P01 HD033113 · United States
NICHD NIH HHS · P01 HD033113-12 · United States
NICHD NIH HHS · P01 HD33113-12 · United States
External Links
PubMed source DOI: 10.1002/ajmg.a.32652 PMC Full Text View journal details
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