Haploinsufficiency of BAZ1B contributes to Williams syndrome through transcriptional dysregulation of neurodevelopmental pathways.

@article{Lalli2016HaploinsufficiencyOB,
  title={Haploinsufficiency of BAZ1B contributes to Williams syndrome through transcriptional dysregulation of neurodevelopmental pathways.},
  author={Matthew A. Lalli and Jiwon Jang and Joo-Hye C. Park and Yidi Wang and Elmer Guzman and Hongjun R Zhou and Morgane Audouard and Daniel C Bridges and K. Ruiz Tovar and Sorina Mihaela Papuc and Andreea Tutulan-Cunita and Yadong Huang and Magdalena Budisteanu and Aurora Arghir and Kenneth S. Kosik},
  journal={Human molecular genetics},
  year={2016},
  volume={25 7},
  pages={
          1294-306
        }
}
Williams syndrome (WS) is a neurodevelopmental disorder caused by a genomic deletion of ∼28 genes that results in a cognitive and behavioral profile marked by overall intellectual impairment with relative strength in expressive language and hypersocial behavior. Advancements in protocols for neuron differentiation from induced pluripotent stem cells allowed us to elucidate the molecular circuitry underpinning the ontogeny of WS. In patient-derived stem cells and neurons, we determined the… 
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BAZ2B haploinsufficiency as a cause of developmental delay, intellectual disability, and autism spectrum disorder
TLDR
High level of functional convergence during fetal cortical development between BAZ2B and genes known to cause autism spectrum disorder (ASD) and neurodevelopmental disorder is demonstrated and suggests that haploinsufficiency of Baz2B causes a neuro developmental disorder, whose cardinal features include DD, ID, and ASD.
The chromatin basis of neurodevelopmental disorders: Rethinking dysfunction along the molecular and temporal axes
Gtf2i and Gtf2ird1 mutation are not sufficient to reproduce mouse phenotypes caused by the Williams Syndrome critical region
TLDR
It is shown that the complete deletion model has deficits across several behavioral domains including social communication, motor functioning, and conditioned fear that are not explained by loss of function mutations in Gtf2i and GTF2ird1.
Rearrangements of 7q11.23: disorders of the epigenome
TLDR
To understand the impact of rearrangements at 7q11.23 on the epigenome, parentof-origin dependent expression of individual genes at this locus, as well as genome-wide DNA are studied.
High-throughput screening identifies histone deacetylase inhibitors that modulate GTF2I expression in 7q11.23 microduplication autism spectrum disorder patient-derived cortical neurons
TLDR
A high-throughput screening of 1478 compounds on patient-derived cortical glutamatergic neurons differentiated from the authors' 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 overriding pathogenic role.
Gtf2i and Gtf2ird1 mutation do not account for the full phenotypic effect of the Williams syndrome critical region in mouse models.
TLDR
It is shown that the complete deletion model has deficits across several behavioral domains including social communication, motor functioning, and conditioned fear that are not explained by loss of function mutations in Gtf2i and GTF2ird1.
Characterizing Vascular and Neuronal Defects in Williams-Beuren Syndrome and 7q11.23 Duplication Syndrome Using Induced Pluripotent Stem Cells
TLDR
In iPSC-derived smooth muscle cells (SMCs), an increase in proliferation and reduction in differentiation among WBS SMCs, while also finding elevated proportions of SMC marker in Dup7 precursors, indicating premature differentiation.
Integrative network analysis reveals biological pathways associated with Williams syndrome
TLDR
Dysregulation of the mRNA/miRNA network involving genes outside of the 7q11.23 region is likely related to the complex phenotypes observed in WS patients.
Williams syndrome
TLDR
An overview of the epidemiology, genetic aetiology, diagnosis, common manifestations and management of this syndrome is provided as well as of how quality of life is affected in individuals with Williams syndrome and their families.
BAZ1B is a candidate gene responsible for hypothyroidism in Williams syndrome.
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References

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TLDR
It is 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.
7q11.23 dosage-dependent dysregulation in human pluripotent stem cells affects transcriptional programs in disease-relevant lineages
TLDR
It is found that 7q11.23 dosage imbalance disrupts transcriptional circuits in disease-relevant pathways beginning in the pluripotent state, and transcriptional dysregulation is specifically caused by dosage imbalances in GTF2I, which encodes a key transcription factor at 7q 11.23 that is associated with the LSD1 repressive chromatin complex and silences its dosage-sensitive targets.
Haploinsufficiency of Gtf2i, a gene deleted in Williams Syndrome, leads to increases in social interactions
TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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