a role for transcription factor gtf2ird2 in executive function in williams-beuren syndrome转录因子的作用在执行功能gtf2ird2 williams-beuren综合症.pdfVIP

A Role for Transcription Factor GTF2IRD2 in Executive Function in Williams-Beuren Syndrome 1 2,3 2,3 2,3 4 Melanie A. Porter *, Carol Dobson-Stone , John B. J. Kwok , Peter R. Schofield , William Beckett , May Tassabehji4* 1 Psychology Department, Macquarie University, Sydney, Australia, 2 Neuroscience Research Australia, Sydney, Australia, 3 School of Medical Sciences, University of New South Wales, Sydney, Australia, 4 Genetic Medicine, University of Manchester St Mary’s Hospital, Manchester, United Kingdom Abstract Executive functions are amongst the most heritable cognitive traits with twin studies indicating a strong genetic origin. However genes associated with this domain are unknown. Our research into the neurodevelopmental disorder Williams- Beuren syndrome (WBS) has identified a gene within the causative recurrent 1.5/1.6 Mb heterozygous microdeletion on chromosome 7q11.23, which may be involved in executive functioning. Comparative genome array screening of 55 WBS patients revealed a larger ,1.8 Mb microdeletion in 18% of cases, which results in the loss of an additional gene, the transcription factor GTF2IRD2. The GTF gene family of transcription factors (GTF2I, GTF2IRD1 and GTF2IRD2) are all highly expressed in the brain, and GTF2I and GTF2IRD1 are involved in the pathogenesis of the cognitive and behavioural phenotypes associated with WBS. A multi-level analysis of cognitive, behavioural and psychological functioning in WBS patients showed that those with slightly larger deletions encompassing GTF2IRD2 were significantly more cognitively impaired in the areas of spatial functioning, social reasoning,