High-throughput screening identifies histone deacetylase inhibitors that modulate GTF2I expression in 7q11.23 microduplication autism spectrum disorder patient-derived cortical neurons.

Molecular Autism
Francesca CavalloGiuseppe Testa

Abstract

Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental condition affecting almost 1% of children, and represents a major unmet medical need with no effective drug treatment available. Duplication at 7q11.23 (7Dup), encompassing 26-28 genes, is one of the best characterized ASD-causing copy number variations and offers unique translational opportunities, because the hemideletion of the same interval causes Williams-Beuren syndrome (WBS), a condition defined by hypersociability and language strengths, thereby providing a unique reference to validate treatments for the ASD symptoms. In the above-indicated interval at 7q11.23, defined as WBS critical region, several genes, such as GTF2I, BAZ1B, CLIP2 and EIF4H, emerged as critical for their role in the pathogenesis of WBS and 7Dup both from mouse models and human studies. We performed a high-throughput screening of 1478 compounds, including central nervous system agents, epigenetic modulators and experimental substances, on patient-derived cortical glutamatergic neurons differentiated from our cohort of induced pluripotent stem cell lines (iPSCs), monitoring the transcriptional modulation of WBS interval genes, with a special focus on GTF2I, in light of its overrid...Continue Reading

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Citations

Feb 21, 2021·Current Opinion in Genetics & Development·Lucy R Osborne, Carolyn B Mervis
Aug 20, 2021·Neuroscience Research·Takanobu Nakazawa

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Methods Mentioned

BETA
Transfection
PCR
protein assay

Software Mentioned

ImageLab
Qbase +
QBase Biogazelle
PRISM
EVOware®
GraphPad
TECAN
QuantStudio
Cellomics

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