Mutations in EBF3 disturb transcriptional profiles and cause intellectual disability, ataxia and facial dysmorphism
Transcriptomics Dataset
FAIR Metrics
0 evaluations
General Information
| Accession | GSE90682 |
| Title | Mutations in EBF3 disturb transcriptional profiles and cause intellectual disability, ataxia and facial dysmorphism |
| Description | From a GeneMatcher-enabled international collaboration, we identified ten individuals with intellectual disability, speech delay, ataxia and facial dysmorphism carrying a deleterious variant in the EBF3 (Early B-cell Factor 3) gene detected by whole-exome sequencing. Five missense, two nonsense, one 9-bp duplication, and one splice-site variant in EBF3 were found; the mutation occurred de novo in eight individuals, and the missense variant c.625C>T [p.(Arg209Trp)] was inherited by two affected siblings from their healthy mother who is a mosaic. EBF3 belongs to the early B-cell factor family (also known as Olf, COE, or O/E) and encodes a transcription factor involved in neuronal differentiation and maturation. Structural assessment predicts damaging effects of the five amino acid substitutions on DNA-binding of EBF3. Transient expression of EBF3 mutant proteins in HEK 293T cells revealed mislocalization of all but one mutant in the cytoplasm in addition to nuclear localization. By transactivation assays, all EBF3 mutants showed significantly reduced or no ability to activate transcription of the CDKN1A reporter gene, and EBF3 mutant proteins were less tightly associated with chromatin as demonstrated by in situ subcellular fractionation experiments. Finally, RNA-seq and ChIP-seq experiments demonstrate that EBF3 acts as a transcriptional regulator and EBF3 mutant protein had reduced genome-wide DNA binding and gene regulatory activity. Our findings demonstrate that variants that disrupt EBF3-mediated transcriptional regulation cause intellectual disability and developmental delay, and are present in ~0.1%% of individuals with unexplained neurodevelopmental disorders. |
| Landing Page | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE90682 |
| Repository | Gene Expression Omnibus |
Related Datasets
GSE48159
Mapping ER genomic binding sites reveals unique genomic features and identifies EBF1 as an ER interactor [Gro-Seq]
1
GSE69227
Combined heterozygous loss of Ebf1 and Pax5 allows for T-lineage conversion of B-cell progenitors
1
Tools
used to analyze the dataset
Canned Analyses
generated with the dataset
FAIR Evaluation
Sorry, you must be signed in to evaluate this object.
