Search results for " deletion"
showing 10 items of 361 documents
Tetraspanin CD151 Promotes Initial Events in Human Cytomegalovirus Infection.
2016
ABSTRACT Human cytomegalovirus (HCMV), a betaherpesvirus, can cause life-threatening disease in immunocompromised individuals. Viral envelope glycoproteins that mediate binding to and penetration into target cells have been identified previously. In contrast, cellular proteins supporting HCMV during entry are largely unknown. In order to systematically identify host genes affecting initial steps of HCMV infection, a targeted RNA interference screen of 96 cellular genes was performed in endothelial cells by use of a virus strain expressing the full set of known glycoprotein H and L (gH/gL) complexes. The approach yielded five proviral host factors from different protein families and eight an…
Oligodendrocytes control potassium accumulation in white matter and seizure susceptibility
2018
Oligodendrocytes Control Potassium Accumulation in White Matter and Seizure Susceptibility.Larson VA, Mironova Y, Vanderpool KG, Waisman A, Rash JE, Agarwal A, Bergles DE. Elife. 2018 Mar 29;7. pii: e34829. doi: 10.7554/eLife.34829.The inwardly rectifying K+ channel Kir4.1 is broadly expressed by central nervous system glia and deficits in Kir4.1 lead to seizures and myelin vacuolization. However, the role of oligodendrocyte Kir4.1 channels in controlling myelination and K+ clearance in white matter has not been defined. Here, we show that selective deletion of Kir4.1 from oligodendrocyte progenitors or mature oligodendrocytes did not impair their development or disrupt the structure of mye…
Intratumoral immunosuppression profiles in 11q-deleted neuroblastomas provide new potential therapeutic targets
2021
In this issue, Coronado et al. attempt to improve our understanding of the factors affecting the response to immunotherapy in a large subset of high‐risk neuroblastoma with hemizygous deletion of chromosome 11q. By using several computational approaches, the authors study potential transcriptional and post‐transcriptional pathways that may affect the response to immunotherapy and further be leveraged therapeutically in a biomarker‐directed fashion.
Heterozygous deletion of the LRFN2 gene is associated with working memory deficits
2016
International audience; Learning disabilities (LDs) are a clinically and genetically heterogeneous group of diseases. Array-CGH and high-throughput sequencing have dramatically expanded the number of genes implicated in isolated intellectual disabilities and LDs, highlighting the implication of neuron-specific post-mitotic transcription factors and synaptic proteins as candidate genes. We report a unique family diagnosed with autosomal dominant learning disability and a 6p21 microdeletion segregating in three patients. The 870 kb microdeletion encompassed the brain-expressed gene LRFN2, which encodes for a synaptic cell adhesion molecule. Neuropsychological assessment identified selective w…
12q14.3 microdeletion involving HMGA2 gene cause a Silver-Russell syndrome-like phenotype: a case report and review of the literature
2020
Abstract Background Silver-Russell Syndrome (SRS) is a genetic disorder characterized by intrauterine and postnatal growth restriction and normal head circumference with consequent relative macrocephaly. Addictional findings are protruding forehead in early life, body asymmetry (of upper and lower limbs) and substantial feeding difficulties. Although several genetic mechanisms that cause the syndrome are known, more than 40% of patients with a SRS-like phenotype remain without an etiological diagnosis. In the last few years, different clinical reports have suggested that mutations or deletions of the HMGA2 gene can be responsible for a SRS-like phenotype in patients with negative results of…
Endothelial Dab1 signaling orchestrates neuro-glia-vessel communication in the central nervous system.
2018
Developing the bloodbrain barrier During development, signals need to be dynamically integrated by endothelial cells, neurons, and glia to achieve functional neuro-glia-vascular units in the central nervous system. During cortical development, neuronal Dab1 and ApoER2 receptors respond to a guidance cue called reelin. Studying mice, Segarra et al. found that Dab1 and ApoER2 are also expressed in endothelial cells (see the Perspective by Thomas). The integration of reelin signaling in endothelial cells and neurons facilitates the communication between vessels, glia, and neurons that is necessary for the correct positioning of neurons during cortical development. This integration is also impo…
Functional hypoxia drives neuroplasticity and neurogenesis via brain erythropoietin.
2020
Erythropoietin (EPO), named after its role in hematopoiesis, is also expressed in mammalian brain. In clinical settings, recombinant EPO treatment has revealed a remarkable improvement of cognition, but underlying mechanisms have remained obscure. Here, we show with a novel line of reporter mice that cognitive challenge induces local/endogenous hypoxia in hippocampal pyramidal neurons, hence enhancing expression of EPO and EPO receptor (EPOR). High-dose EPO administration, amplifying auto/paracrine EPO/EPOR signaling, prompts the emergence of new CA1 neurons and enhanced dendritic spine densities. Single-cell sequencing reveals rapid increase in newly differentiating neurons. Importantly, i…
Benign nocturnal alternating hemiplegia of childhood
2018
Objective: To describe the clinical spectrum of benign nocturnal alternating hemiplegia of childhood (BNAHC) including long-term follow-up data of previously published cases and to propose an underlying genetic cause of this disorder. Methods: We studied the medical data of two novel patients, reviewed the literature on BNAHC, and gathered information of the most recent follow-up of published cases regarding the course of episodes, further development, attempted drugs, ancillary investigations, and sequelae. Results: All patients, i.e. two novel cases and twelve patients identified in the literature (13 boys, 1 girl, age at onset four months to three years), experienced episodes of hemipleg…
Dominant variants in the splicing factor PUF60 cause a recognizable syndrome with intellectual disability, heart defects and short stature
2016
Item does not contain fulltext Verheij syndrome, also called 8q24.3 microdeletion syndrome, is a rare condition characterized by ante- and postnatal growth retardation, microcephaly, vertebral anomalies, joint laxity/dislocation, developmental delay (DD), cardiac and renal defects and dysmorphic features. Recently, PUF60 (Poly-U Binding Splicing Factor 60 kDa), which encodes a component of the spliceosome, has been discussed as the best candidate gene for the Verheij syndrome phenotype, regarding the cardiac and short stature phenotype. To date, only one patient has been reported with a de novo variant in PUF60 that probably affects function (c.505C>T leading to p.(His169Tyr)) associated wi…
Myeloid Cells Restrict MCMV and Drive Stress- Induced Extramedullary Hematopoiesis through STAT1
2019
Cytomegalovirus (CMV) has a high prevalence worldwide, is often fatal for immunocompromised patients, and causes bone marrow suppression. Deficiency of signal transducer and activator of transcription 1 (STAT1) results in severely impaired antiviral immunity. We have used cell- type restricted deletion of Stat1 to determine the importance of myeloid cell activity for the defense against murine CMV (MCMV). We show that myeloid STAT1 limits MCMV burden and infection- associated pathology in the spleen but does not affect ultimate clearance of infection. Unexpectedly, we found an essential role of myeloid STAT1 in the induction of extramedullary hematopoiesis (EMH). The EMH- promoting function…