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Williams-Beuren syndrome: typical deletions versus atypical deletions of the 7q11.23 region

ABSTRACT: We have performed comparative transcriptome profile from lymphoblastoid cell lines from four Williams-Beuren syndrome patients and two patients with partial deletions of the region. The goal was to find deregulated genes specifically in WBS versus atypical deletions, and to determine the biological pathways affected in WBS patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE18188 | GEO | 2010/09/09

SECONDARY ACCESSION(S): PRJNA119549

REPOSITORIES: GEO

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Williams-Beuren syndrome: typical deletions versus atypical deletions of the 7q11.23 region

Project description:We have performed comparative transcriptome profile from lymphoblastoid cell lines from four Williams-Beuren syndrome patients and two patients with partial deletions of the region. The goal was to find deregulated genes specifically in WBS versus atypical deletions, and to determine the biological pathways affected in WBS patients. 6 samples were hybridized twice each: once labeled with Cy5 and once labeled with Cy3 (dye-swap). Each sample was hybridized against a pool of five controls of the same gender.

2010-09-09 | E-GEOD-18188 | biostudies-arrayexpress

Expression profiling in Williams-Beuren Syndrome patient fibroblast cell lines

2011-01-31 | GSE16715 | GEO

The deletion of the Williams-Beuren Syndrome critical region dysregulate the expression of miR379-410 miRNA members in human isogenic iNeurons

Project description:While psychiatric disorders (e.g., schizophrenia) and autism spectrum disorders (ASD) are typically associated with a deficit in social behavior, the opposite trait of hypersociability is exhibited by individuals with specific neurodevelopmental disorders, e.g., Angelman Syndrome (AS) and Williams-Beuren Syndrome (WBS). We have recently reported that the deletion of the miR379-410 cluster in mice led to hypersocial behavior. To study the roles of this miRNA cluster in the context of WBS, we sent for smallRNA sequencing RNA isolated from isogenic human iPSC-derived neurons harboring a deletion present in Williams-Beuren-Syndrome patients (7q11.23). Specifically, we found that members of the miR379-410 cluster were strikingly overrepresented among downregulated miRNAs in iNeurons harboring a deletion of the WBS critical region. Thus, we obtained the first evidence for the pathophysiological significance of the miR379-410 miRNA cluster in the context of WBS. We conclude that targeting this novel pathway could have therapeutic potential for WBS and other neurodevelopmental conditions characterized by social impairments.

2023-11-15 | GSE247766 | GEO

Expression profiling in Williams-Beuren Syndrome patient fibroblast cell lines

Project description:Williams-Beuren Syndrome (WBS) is a neurodevelopmental disorder caused by aa 1.5 Mb microdeletion on human chromosome 7. Although the molecular cause of the disorder is well-established, little is known about the global impact of the deletion on gene expression. Here we profiled the transcriptomes of fibroblast cell lines from 8 young girls with WBS, and 9 sex- and age-matched control individuals Keywords: disease state analysis, gene expression profiling Skin fibroblast of 8 WBS and 9 control individuals were obtained from the cell culture collections of the “Centre de Biotechnologie Cellulaire, Hospices Civils de Lyon, Hôpital Debrousse”, Lyon, France. Appropriate informed consent was obtained for each sample by the physicians in charge. Human skin fibroblasts were grown in HAM F-10, supplemented with 10% fetal bovine serum and 1% antibiotics (Invitrogen). Total RNA was prepared using TriZOL Reagent (Invitrogen) and RNeasy Mini Columns (Qiagen) according to the manufacturers’ instructions.

2011-01-31 | E-GEOD-16715 | biostudies-arrayexpress

Human induced pluripotent stem cell derived neurons as a model for Williams-Beuren syndrome

Project description:Williams-Beuren Syndrome (WBS) is caused by the microdeletion of approximately 25 genes on chromosome 7q11.23, and is characterized by a spectrum of cognitive and behavioural features. We generated cortical neurons from a WBS individual and unaffected (WT) control by directed differentiation of induced pluripotent stem cells (iPSCs). Single cell mRNA analyses and immunostaining demonstrated very efficient production of differentiated cells expressing markers of mature neurons of mixed subtypes and from multiple cortical layers. We found that passive membrane properties were comparable in these WBS and WT neurons, but there was a profound alteration in action potentials, with significantly prolonged WBS repolarization times and a WBS deficit in voltage-activated K+ currents. Miniature excitatory synaptic currents were normal, indicating that unitary excitatory synaptic transmission was not altered. Gene expression profiling identified 136 negatively enriched gene sets in WBS compared to WT neurons. These genes are involved in synaptic transmission and assembly, cation transport, axon guidance and elastic fibre pathways, and some encode ion channels. Our findings provide insight into gene dysregulation and electrophysiological defects in WBS patient neurons.

2016-03-29 | GSE67535 | GEO

Cannabinoid signaling modulation through JZL184 restores key phenotypes of a mouse model for Williams- Beuren syndrome

Project description:JZL184 treatment restores neurological and cardiac phenotypes of a mouse model of Williams-Beuren syndrome

2022-10-11 | GSE164257 | GEO

Detection of deletions at 7q11.23 in Williams-Beuren syndrome by polymorphic markers.

Project description: Not available

| S-EPMC3129970 | biostudies-literature

GTF2I dosage regulates neuronal differentiation and social behavior in 7q11.23 neurodevelopmental disorders

Project description:Copy number variations at 7q11.23 cause neurodevelopmental disorders with shared and opposite manifestations. Deletion leads to Williams-Beuren syndrome (WBS), while duplication causes 7q11.23 microduplication syndrome (7Dup). Converging evidence indicates GTF2I, from the 7q11.23 locus, is a key mediator of the cognitive-behavioral phenotypes associated with WBS and 7Dup. Here we integrate molecular profiling of patient-derived cortical organoids (COs) and transgenic mouse models to dissect 7q11.23 disease mechanisms. Proteomic and transcriptomic profiling of COs revealed opposite dynamics of neural progenitor proliferation and transcriptional imbalances, leading to precocious excitatory neuron production in 7Dup. The accelerated excitatory neuron production in 7Dup COs could be rescued by GTF2I knockdown. Transgenic mice with Gtf2i duplication recapitulated early neuronal differentiation defects and ASD-like behaviors. Remarkably, inhibition of LSD1, a downstream effector of GTF2I, was sufficient to rescue ASD-like phenotypes. We propose that the GTF2I-LSD1 axis constitutes a molecular pathway amenable to therapeutic intervention.

2024-01-26 | PXD036770 | Pride

Genome-wide maps of chromatin state in Williams-Beuren (WBS), Williams-Beuren Region duplication (WBRdupS), Smith-Magenis (DGS), DiGeorge (DGS) lymphoblastoid cell lines

Project description:Copy number variants (CNV) influence the expression of genes that map not only within, but also on their flanks. To assess the possible mechanism(s) underlying this “neighboring effect”, we compared intrachromosomal interactions and histone modifications in cell lines of patients affected by genomic disorders and control individuals. We detected alteration of intrachromosomal interactions (chromosomal looping) between the loci of affected genes and the rearranged interval using chromosome conformation capture (4C-seq). These results are consistent with the observed gene expression alterations. We also pinpointed concomitant changes in histone modifications between samples. Modified genes were often looping together, possibly forming an interacting cluster. We conclude that large genomic rearrangements can lead to chromatin conformation changes that extend far away from the structural variant, thus possibly modulating expression globally and modifying the phenotype. For example, we observe that the chromatin conformation, histone marks and relative expression levels of the AUTS2 gene, mutations of which are associated with autism and intellectual disabilities, are modified in Williams-Beuren syndrome patients cell lines. Examination of 2 different histone modifications in genomic disorders patients' cell lines.

2013-11-16 | E-GEOD-33784 | biostudies-arrayexpress

RNA-seq of human iPSCs derived neural crest stem cells (NCSCs) upon knock-down of BAZ1B (WSTF), including 3 williams beuren syndrome lines, 1 atypical deletion line, and 3 individuals with 7q11.23 duplication syndrome. Each line has been infected with a scramble, or at least one of two short-hairpins (as described in the coupled paper).

Project description:In order to dissect the role of BAZ1B in the paradigmatic craniofacial dysmorphisms that characterize Williams Beuren Syndrome and the simmetrical genetically opposite 7q11.23 duplication syndrome(7dupASD), we selected a large cohort of NCSCs lines (4 from WBS patients, 3 from 7dupASD patients and 4 from control individuals) to perform transcriptomic profiling. These lines show a clear cranial identity signatures which is crucial to pinpoint the disease pathogenesis, We then knocked-down (KD) BAZ1B via RNA interference in all lines across the three genetic conditions, including also NCSCs derived from a particularly informative atypical WBS patient (atWBS) bearing a partial deletion of the region that spares BAZ1B and six additional genes (see paper). In order to establish a high-resolution gradient of BAZ1B dosages, we selected two distinct shRNA against BAZ1B (i.e., sh1 and sh2) along with a scrambled shRNA sequence (hereafter scr) as negative control, for a total of 32 NCSC lines. KD efficiency was evaluated both at the RNA level by quantitative PCR (qPCR), confirming the attainment of the desired gradient with an overall reduction of about 40% for sh1 and 70% for sh2, as well as reduction at the protein level, as detected by Western blot (see the coupled paper).

2020-02-29 | E-MTAB-8455 | biostudies-arrayexpress

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