Homo sapiens
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PROVIDER: PRJNA131449 | ENA |
REPOSITORIES: ENA
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Project description:Abstract Background Neurexins are proteins located in the presynaptic membrane that bind postsynaptic ligands, neuroligins, neurexophilins, and dystrophoglycan. They exert profound effects on neurological function by mediating signalling across synapses and determining synaptic characteristics through the recruitment of additional proteins for synapse formation. Alterations in neurexin-encoding genes cause cognitive disorders such as autism, developmental delay and schizophrenia. The three neurexin genes in the human genome (NRXN1, NRXN2, and NRXN3) each have two different functional promoters, producing a large (alpha) and small (beta) transcript with corresponding proteins. NRXN1 produces hundreds, perhaps thousands, of different transcripts with differential localization in the CNS. Results We report here the identification of an individual (53825) with mild dysmorphia, severe language disorder, mild intellectual disability, attention deficit hyperactivity disorder (ADHD), and a mood disorder. Genomic analysis by Affymetrix 6.0 Gene Chip and FISH (fluorescence in situ hybridization) using probes specific for NRXN1 revealed a hemizygous deletion of approximately 190 Kb, which includes exons 3-5 of NRXN1. This deletion should result in the absence of the vast majority of different NRXN1 alpha transcripts from one of the NRXN1 gene copies, without effecting NRXN1 beta transcription. Copy number analysis of Affymetrix 6.0 SNP arrays was performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples for pediatric patients. One sample showed partial deletion of NRXN1 alpha; data presented in this Series.
2011-06-24 | E-GEOD-23358 | biostudies-arrayexpress
Project description:Dosage imbalance of NMD genes is associated with intellectual disability
| PRJNA152581 | ENA
Project description:Abstract Background Neurexins are proteins located in the presynaptic membrane that bind postsynaptic ligands, neuroligins, neurexophilins, and dystrophoglycan. They exert profound effects on neurological function by mediating signalling across synapses and determining synaptic characteristics through the recruitment of additional proteins for synapse formation. Alterations in neurexin-encoding genes cause cognitive disorders such as autism, developmental delay and schizophrenia. The three neurexin genes in the human genome (NRXN1, NRXN2, and NRXN3) each have two different functional promoters, producing a large (alpha) and small (beta) transcript with corresponding proteins. NRXN1 produces hundreds, perhaps thousands, of different transcripts with differential localization in the CNS. Results We report here the identification of an individual (53825) with mild dysmorphia, severe language disorder, mild intellectual disability, attention deficit hyperactivity disorder (ADHD), and a mood disorder. Genomic analysis by Affymetrix 6.0 Gene Chip and FISH (fluorescence in situ hybridization) using probes specific for NRXN1 revealed a hemizygous deletion of approximately 190 Kb, which includes exons 3-5 of NRXN1. This deletion should result in the absence of the vast majority of different NRXN1 alpha transcripts from one of the NRXN1 gene copies, without effecting NRXN1 beta transcription.
2011-06-25 | GSE23358 | GEO
Project description:Large Xq22.3 deletion in Czech family inherited from unaffaceted mother leading to manifestation of X-linked contiguous gene deletion syndrome known as Alport syndrome with intellectual disability (ATS-ID) or AMME complex (OMIM #300194)
2019-12-02 | E-MTAB-8324 | biostudies-arrayexpress
Project description:10 Intellectual Disability samples for clinically relevant CNV detection
| PRJNA197143 | ENA
Project description:The Psychiatric Risk Gene Transcription Factor 4 (TCF4) Regulates Neurodevelopmental Pathways Associated With Schizophrenia, Autism, and Intellectual Disability
| PRJNA380103 | ENA
Project description:Loss of function of FMR2 due to either hypermethylation of the CpG island as a consequence of the expansion of the CCG repeat near its transcription start site, or internal deletion of FMR2 is considered to be the major cause of FRAXE fragile site associated intellectual disability. FMR2 was shown to be a potent transcription activator as well as an RNA binding protein capable of regulating alternative splicing. Using whole transcriptome approach, we aimed to identify genes regulated by FMR2 and to study their contribution to the underlying causes of intellectual disability in the patients. We subjected total RNA extracted from fibroblasts of FRAXE patients (n=8), and unrelated controls (n=4) to Affymetrix Human Exon 1.0 ST array
2012-05-31 | E-GEOD-27953 | biostudies-arrayexpress
Project description:We implicated the X-chromosome THOC2 gene, which encodes largest subunit of the highly-conserved TREX (Transcription-Export) complex, in a clinically variable neurodevelopmental disorder with intellectual disability as the core phenotype. To study how compromised function of this essential eukaryotic gene leads to NDD outcomes, we generated a clinically-relevant mouse model based on a hypomorphic Thoc2 exon 37-38 deletion variant of a patient with ID, speech delay, hypotonia, and microcephaly. The Thoc2 exon 37-38 deletion male (Thoc2/Y) mice recapitulate the core phenotypes of THOC2 syndrome including smaller size and weight, and significant deficits in spatial learning, working memory and sensorimotor functions. The Thoc2/Y mouse brain development is significantly impacted by compromised THOC2/TREX function resulting in R-loop accumulation, DNA damage and consequent cell death. Overall, we suggest that perturbed R-loop homeostasis, in stem cells and/or differentiated cells in mice and the patient, and DNA damage-associated functional alterations are at the root of THOC2 syndrome.
2024-02-12 | PXD040358 | Pride
Project description:Genetic perturbations of the transcription factor, Forkhead Box P1 (FOXP1), occur in patients with autism spectrum disorder who have an increased risk for comorbidity with intellectual disability. Recent work has begun to reveal an important role for Foxp1 in brain development, but the brain region-specific contribution of Foxp1 to autism and intellectual disability phenotypes has yet to be fully determined. Here, we characterize Foxp1 conditional knockout (Foxp1cKO) mice with loss of Foxp1 in the pyramidal neurons of the neocortex and the CA1/CA2 subfields of the hippocampus. Foxp1cKO mice exhibit behavioral phenotypes that are relevant to autism spectrum disorder, including hyperactivity, increased anxiety, and decreased sociability. In addition, Foxp1cKO mice have gross deficits in learning and memory tasks that are relevant to intellectual disability. Using a genome-wide approach, we identified genes differentially expressed in the hippocampus of Foxp1cKO mice that are associated with synaptic function and physiology that could represent molecular networks related to the observed behavioral deficits. Finally, we observed reduced maintenance of long-term potentiation in the CA1 subfield of these animals. Together, these data suggest that expression of Foxp1 in pyramidal neurons of the forebrain is important for regulating gene expression pathways that contribute to specific behaviors relevant to autism and intellectual disability. In particular, Foxp1 regulation of gene expression in the hippocampus appears to be crucial for normal CA1 physiology and spatial learning.
2018-02-13 | GSE97181 | GEO
Project description:Fragile X syndrome (FXS), caused by mutations in fragile X mental retardation 1 gene (FMR1), is a prevailing genetic disorder of intellectual disability and autism. Analysis of transcriptome outcome (differentially expressed genes between WT and Fmr1 KO hippocampal neuron) associated with FXS reveal promising value of gene signature-based computation in repurposing drugs for potential practical treatment.
2019-12-05 | GSE114015 | GEO