A role for transcription factor GTF2IRD2 in executive function in Williams-Beuren syndrome
| Autor: | May Tassabehji, Peter R. Schofield, John B.J. Kwok, William Beckett, Melanie A. Porter, Carol Dobson-Stone |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Williams Syndrome Emotions Muscle Proteins lcsh:Medicine Social and Behavioral Sciences Chromosomal Disorders Habits Executive Function Transcription Factors TFII 0302 clinical medicine Neurodevelopmental disorder Cognition Human Performance Psychology lcsh:Science Problem Solving Genetics 0303 health sciences Multidisciplinary Cognitive flexibility Neuropsychology Chromosomal Deletions and Duplications Nuclear Proteins Executive functions 3. Good health Mental Health Medicine Female Williams syndrome Chromosome Deletion Chromosomes Human Pair 7 Research Article Social Psychology Cognitive neuroscience Biology 03 medical and health sciences Transcription Factors TFIII medicine Learning Humans Genetic Testing Amino Acid Sequence Genetic Association Studies 030304 developmental biology Clinical Genetics Behavior Motivation Verbal Behavior lcsh:R Cognitive Psychology Reasoning medicine.disease Human Intelligence Trans-Activators lcsh:Q Attention (Behavior) Sequence Alignment 030217 neurology & neurosurgery Executive dysfunction |
| Zdroj: | PLoS ONE, Vol 7, Iss 10, p e47457 (2012) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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, and cognitive flexibility (a form of executive functioning). They also displayed significantly more obsessions and externalizing behaviours, a likely manifestation of poor cognitive flexibility and executive dysfunction. We provide the first evidence for a role for GTF2IRD2 in higher-level (executive functioning) abilities and highlight the importance of integrating detailed molecular characterisation of patients with comprehensive neuropsychological profiling to uncover additional genotype-phenotype correlations. The identification of specific genes which contribute to executive function has important neuropsychological implications in the treatment of patients with conditions like WBS, and will allow further studies into their mechanism of action. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|