Investigating the Function of GTF2I and its Contribution to the Williams-Beuren Syndrome Neurological Profile

Williams-Beuren Syndrome (WBS) is a genetic neurodevelopmental disorder caused by the deletion of 25 protein-coding genes at chromosome 7q11.23. It is associated with a highly penetrant constellation of phenotypes, including aortic stenoses, characteristic facial features, and unique cognitive and behaviour profiles. I hypothesize that the gene GTF2I, a putative transcription factor, plays a role in signaling pathways that affect neuronal function and contribute to the WBS neurological profile. Genome-wide expression analysis of WBS patient-derived induced pluripotent stem cells and cortical neurons isolated from mice with a duplication or deletion of Gtf2i identified moderate changes in the expression of a few genes. Additionally, affinity purification and tandem mass spectrometry of GFP-tagged GTF2I validated a previously identified interaction with ZMYM3, a candidate for X-linked intellectual disability. Future studies to determine the consequence of this interaction in the brain will assist in characterizing GTF2I function in neurons and its contribution to WBS phenotypes.M.Sc