Talk:Williams Syndrome
| About Discussion Pages |
|---|
Glossary Links
Cite this page: Hill, M.A. (2024, April 18) Embryology Williams Syndrome. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Williams_Syndrome |
2011
Using novel control groups to dissect the amygdala's role in Williams Syndrome
Dev Cogn Neurosci. 2011 Jul;1(3):295-304.
Thornton-Wells TA, Avery SN, Blackford JU. Source Center for Human Genetics Research, Vanderbilt University Medical Center, 519 Light Hall, Nashville, TN 37232.
Abstract
Williams syndrome is a neurodevelopmental disorder with an intriguing behavioral phenotype-hypersociability combined with significant non-social fears. Previous studies have demonstrated abnormalities in amygdala function in individuals with Williams syndrome compared to typically-developing controls. However, it remains unclear whether the findings are related to the atypical neurodevelopment of Williams syndrome, or are also associated with behavioral traits at the extreme end of a normal continuum. We used functional magnetic resonance imaging (fMRI) to compare amygdala blood-oxygenation-level-dependent (BOLD) responses to non-social and social images in individuals with Williams syndrome compared to either individuals with inhibited temperament (high non-social fear) or individuals with uninhibited temperament (high sociability). Individuals with Williams syndrome had larger amygdala BOLD responses when viewing the non-social fear images than the inhibited temperament control group. In contrast, when viewing both fear and neutral social images, individuals with Williams syndrome did not show smaller amygdala BOLD responses relative to the uninhibited temperament control group, but instead had amygdala responses proportionate to their sociability. These results suggest heightened amygdala response to non-social fear images is characteristic of WS, whereas, variability in amygdala response to social fear images is proportionate to, and might be explained by, levels of trait sociability.
PMID: 21731599 http://www.ncbi.nlm.nih.gov/pubmed/21731599
2010
Negative autoregulation of GTF2IRD1 in Williams-Beuren syndrome via a novel DNA binding mechanism
J Biol Chem. 2010 Feb 12;285(7):4715-24. Epub 2009 Dec 9.
Palmer SJ, Santucci N, Widagdo J, Bontempo SJ, Taylor KM, Tay ES, Hook J, Lemckert F, Gunning PW, Hardeman EC. Source Department of Anatomy, School of Medical Sciences, The University of New South Wales, Sydney 2052, Australia. s.palmer@unsw.edu.au
Abstract
The GTF2IRD1 gene is of principal interest to the study of Williams-Beuren syndrome (WBS). This neurodevelopmental disorder results from the hemizygous deletion of a region of chromosome 7q11.23 containing 28 genes including GTF2IRD1. WBS is thought to be caused by haploinsufficiency of certain dosage-sensitive genes within the deleted region, and the feature of supravalvular aortic stenosis (SVAS) has been attributed to reduced elastin caused by deletion of ELN. Human genetic mapping data have implicated two related genes GTF2IRD1 and GTF2I in the cause of some the key features of WBS, including craniofacial dysmorphology, hypersociability, and visuospatial deficits. Mice with mutations of the Gtf2ird1 allele show evidence of craniofacial abnormalities and behavioral changes. Here we show the existence of a negative autoregulatory mechanism that controls the level of GTF2IRD1 transcription via direct binding of the GTF2IRD1 protein to a highly conserved region of the GTF2IRD1 promoter containing an array of three binding sites. The affinity for this protein-DNA interaction is critically dependent upon multiple interactions between separate domains of the protein and at least two of the DNA binding sites. This autoregulatory mechanism leads to dosage compensation of GTF2IRD1 transcription in WBS patients. The GTF2IRD1 promoter represents the first established in vivo gene target of the GTF2IRD1 protein, and we use it to model its DNA interaction capabilities.
PMID: 20007321 http://www.ncbi.nlm.nih.gov/pubmed/20007321
