A977d992-cb01-446a-8f34-3ca6a84ebe87 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001004865 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:This dataset contains Whole Genome Sequencing and, if available, RNA-sequencing and/or ATAC-sequencing data obtained from PBMCs derived from blood samples of two patients with intellectual disability and/or multiple congenital anomalies and eight parents included in the University Medical Center Utrecht (The Netherlands). Data access is closed.
| EGAD00001004864 | EGA
Project description:We identified a missense variant in PSMD12 gene, recently associated to an emerging syndromic form of NDD, in a patient with intellectual disability/speech delay, congenital anomalies and facial dysmorphisms. The variant described herein is useful to expand the molecular spectrum of heterozygous PSMD12 mutations and to provide insight into the molecular pathogenesis of this new condition since it is, to the best of our knowledge, the first missense substitution to date reported in medical literature. Finally, our patient is the one with the most detailed dysmorphic characterization and for this reason useful to start defining a typical facial gestalt that addresses the diagnosis.
2019-06-01 | E-MTAB-7977 | biostudies-arrayexpress
Project description:Pathogenic variants in multiple X-linked genes have been implicated in syndromic and non- syndromic intellectual disability disorders. The gene ZFX on Xp22.11 encodes a transcription factor that has been linked to diverse processes including oncogenesis and development, but germline variants have not previously been reported in association with disease. Here, we present clinical and molecular characterization of 18 patients with germline ZFX variants. Exome or genome sequencing revealed 11 variants in 18 subjects (14 males and 4 females) from 16 unrelated families. Four missense variants were identified in 11 subjects, with seven frameshift variants in the remaining individuals. Clinical findings included developmental delay/intellectual disability, behavioral abnormalities, hypotonia, and congenital anomalies. Overlapping and recurrent facial features were identified in all subjects, including thickening and medial broadening of eyebrows, variations in the shape of the face, external eye abnormalities, smooth and/or long philtrum and ear abnormalities. Hyperparathyroidism was found in 4 families with missense variants and enrichment of different types of tumors was also observed. In molecular studies, variants in the DNA-binding domain demonstrated differential expression of target genes relative to wild-type ZFX in cultured cells, suggesting a gain or loss of transcriptional activity. Additionally, a zebrafish model of ZFX loss displayed an altered behavioral phenotype, supporting the pathogenicity of predicted loss- of-function frameshift variants. Our clinical and experimental data support that variants in ZFX cause a novel X-linked intellectual disability syndrome characterized by a recurrent facial gestalt, neurocognitive and behavioral abnormalities, and an increased risk for congenital anomalies and hyperparathyroidism.
2023-11-30 | GSE218689 | GEO
Project description:Pathogenic variants in multiple X-linked genes have been implicated in syndromic and non- syndromic intellectual disability disorders. The gene ZFX on Xp22.11 encodes a transcription factor that has been linked to diverse processes including oncogenesis and development, but germline variants have not previously been reported in association with disease. Here, we present clinical and molecular characterization of 18 patients with germline ZFX variants. Exome or genome sequencing revealed 11 variants in 18 subjects (14 males and 4 females) from 16 unrelated families. Four missense variants were identified in 11 subjects, with seven frameshift variants in the remaining individuals. Clinical findings included developmental delay/intellectual disability, behavioral abnormalities, hypotonia, and congenital anomalies. Overlapping and recurrent facial features were identified in all subjects, including thickening and medial broadening of eyebrows, variations in the shape of the face, external eye abnormalities, smooth and/or long philtrum and ear abnormalities. Hyperparathyroidism was found in 4 families with missense variants and enrichment of different types of tumors was also observed. In molecular studies, variants in the DNA-binding domain demonstrated differential expression of target genes relative to wild-type ZFX in cultured cells, suggesting a gain or loss of transcriptional activity. Additionally, a zebrafish model of ZFX loss displayed an altered behavioral phenotype, supporting the pathogenicity of predicted loss- of-function frameshift variants. Our clinical and experimental data support that variants in ZFX cause a novel X-linked intellectual disability syndrome characterized by a recurrent facial gestalt, neurocognitive and behavioral abnormalities, and an increased risk for congenital anomalies and hyperparathyroidism.
2023-11-30 | GSE218688 | GEO
Project description:Identifying causes of sporadic intellectual disability remains a considerable medical challenge. Here, we demonstrate that null mutations in the NONO gene, a member of the Drosophila Behavior Human Splicing (DBHS) protein family, are a novel cause of X-linked syndromic intellectual disability. Comparing humans to Nono-deficient mice revealed related behavioral and craniofacial anomalies, as well as global transcriptional dysregulation. Nono-deficient mice also showed deregulation of a large number of synaptic transcripts, causing a disorganization of inhibitory synapses, with impaired postsynaptic scaffolding of gephyrin. Alteration of gephyrin clustering could be rescued by over-expression of Gabra2 in NONO-compromised neurons. These findings link NONO to intellectual disability and first highlight the key role of DBHS proteins in functional organization of GABAergic synapses.
2015-09-02 | E-MTAB-2895 | biostudies-arrayexpress
Project description:Identifying causes of sporadic intellectual disability remains a considerable medical challenge. Here, we demonstrate that null mutations in the NONO gene, a member of the Drosophila Behavior Human Splicing (DBHS) protein family, are a novel cause of X-linked syndromic intellectual disability. Comparing humans to Nono-deficient mice revealed related behavioral and craniofacial anomalies, as well as global transcriptional dysregulation. Nono-deficient mice also showed deregulation of a large number of synaptic transcripts, causing a disorganization of inhibitory synapses, with impaired postsynaptic scaffolding of gephyrin. Alteration of gephyrin clustering could be rescued by over-expression of Gabra2 in NONO-compromised neurons. These findings link NONO to intellectual disability and first highlight the key role of DBHS proteins in functional organization of GABAergic synapses.
2015-09-02 | E-MTAB-2894 | biostudies-arrayexpress
Project description:Intellectual disability (ID) is a clinically important disease and a most prevalent neurodevelopmental disorder. The etiology and pathogenesis of ID are poorly recognized. Exome sequencing revealed a homozygous missense mutation in the POLR3B gene in a consanguineous family with three Intellectual disability with craniofacal anomalies patients. POLR3B gene encoding the second largest subunit of RNA polymerase III. To explore how genetic variants alter cell expression in ID patients, RNA sequencing on blood samples was performed and to obtain insights into the biological pathways influenced by POLR3B mutation, we applied our RNA-Seq data to several gene ontology programs such as ToppGene, Enrichr, KEGG. We detected a significant decrease expression of several spliceosomal RNAs, ribosomal proteins and transcription factors in our ID patients. We hypothesize that POLR3B mutation dysregulates the expression of some important transcription factors, ribosomal and spliceosomal genes and impairments in protein synthesis and splicing mediated in part by transcription factors such as FOXC2, GATA1, .. contribute to impaired neuronal function and concurrence of intellectual disability and craniofacial anomalies in our patients. Our study highlights the emerging role of spliceosome and ribosomal proteins in intellectual disability.
2022-04-27 | GSE184234 | GEO
Project description:Ash1l encodes a histone methyltransferase, a member of the trithorax group proteins, which regulates developmental essential gene expression by catalyzing H3K36 methylation and counteracting polycomb silencing. Accumulating reports suggest the loss-of-function mutants in Ash1l gene are associated with intellectual disability (ID), attention-deficit/hyperactivity (ADHD), autism spectrum disorder (ASD), Tourette syndrome (TS) and multiple congenital anomalies (MCA). We performed transcriptional profiling of dorsal striatum in 1-year-old Ash1l mutant brain via RNA sequencing (RNA-seq). Ash1l haploinsufficiency induces transcription alternation of genes involved in synaptic function and cortical development, implicating the deficits in synapse pruning and behavior in adult mice.
2022-01-25 | GSE173502 | GEO
Project description:Intellectual disability is a neurodevelopmental disorder that affects 2-3% of the general population. Syndromic forms of intellectual disability frequently have a genetic basis and are often accompanied by additional developmental anomalies. Pathogenic variants in components of TATA-binding protein associated factors (TAFs) have recently been identified in a subset of patients with intellectual disability, craniofacial hypoplasia, and congenital heart disease. This syndrome has been termed as a TAFopathy and includes mutations in TATA binding protein (TBP), TAF1, TAF2, and TAF6. The underlying mechanism by which TAFopathies give rise to neurodevelopmental, craniofacial, and cardiac abnormalities remains to be defined. Through a forward genetic screen in zebrafish, we have recovered a recessive mutant phenotype characterized by craniofacial hypoplasia, ventricular hypoplasia, heart failure at 96 hours post-fertilization and lethality, and show it is caused by a nonsense mutation in taf5. CRISPR/CAS9 mediated gene editing revealed that these defects where phenocopied by mutations in taf1 and taf5. Mechanistically, taf5-/- zebrafish displayed misregulation in metabolic gene expression and metabolism as evidenced by RNA sequencing, respiration assays, and metabolite studies. Collectively, these findings suggest that the TAF complex may contribute to neurologic, craniofacial, and cardiac development through regulation of metabolism.
2023-04-30 | GSE230183 | GEO
Project description:This dataset contains Whole Genome Sequencing and, if available, RNA-sequencing and/or ATAC-sequencing data of 17 lymphoblastoid cell lines derived from patients with complex genomic rearrangements. Patients have phenotypes in category of intellectual disability and/or multiple congenital anomalies. Data access is closed.
| EGAD00001004866 | EGA