Cerebrovascular diseases in two patients with entire NSD1 deletion.
Ontology highlight
ABSTRACT:
SUBMITTER: Itai T
PROVIDER: S-EPMC8144564 | biostudies-literature | 2021 May
REPOSITORIES: biostudies-literature
Publications
Cerebrovascular diseases in two patients with entire NSD1 deletion.
Itai Toshiyuki T Miyatake Satoko S Hatano Taku T Hattori Nobutaka N Ohno Atsuko A Aoki Yusuke Y Itomi Kazuya K Mori Harushi H Saitsu Hirotomo H Matsumoto Naomichi N
Human genome variation 20210524 1
We describe two patients with NSD1 deletion, who presented with early-onset, or recurrent cerebrovascular diseases (CVDs). A 39-year-old female showed developmental delay and abnormal gait in infancy, and developed slowly-progressive intellectual disability and movement disorders. Brain imaging suggested recurrent parenchymal hemorrhages. A 6-year-old male had tremor as a neonate and brain imaging revealed subdural hematoma and brain contusion. This report suggests possible involvement of CVDs a ...[more]
Similar Datasets
Project description:BackgroundPatent foramen ovale (PFO) is a prevalent cardiac remnant of fetal anatomy that may pose a risk factor for stroke in some patients, while others can present with asymptomatic white matter (WM) lesions. The current study aimed to test the hypothesis that patients with a PFO who have a history of stroke or transient ischemic attack, compared to those without such a history, have a different burden and distribution of cerebral WM hyperintensities. Additionally, we tested the association between PFO morphological characteristics and severity of shunt, and their impact on the occurrence of ischemic cerebral vascular events and on the burden of cerebral WM lesions.Patients and methodsRetrospective, case-control study that included patients with PFO confirmed by transesophageal echocardiography. Right-to-left shunt size was assessed using transcranial Doppler ultrasound. Cerebral MRIs were analyzed for all participants using the semi-automated Quantib NDTM software for the objective quantification of WM lesions. WM lesions volume was compared between patients with and without a history of stroke. Additionally, the anatomical characteristics of PFOs were assessed to explore their relation to stroke occurrence and WM lesions volume.ResultsOf the initial 264 patients diagnosed with PFO, 67 met the inclusion criteria and were included in the analysis. Of them, 62% had a history of PFO-related stroke/TIA. Overall burden of WM lesions, including stroke volume, was not significantly different (p = 0.103). However, after excluding stroke volume, WM lesions volume was significantly higher in patients without stroke (0.27 cm3, IQR 0.03-0.60) compared to those with stroke/TIA (0.08 cm3, IQR 0.02-0.18), p = 0.019. Patients with a history of PFO-related stroke/TIA had a tendency to larger PFO sizes by comparison to those without, in terms of length and height, and exhibited greater right-to-left shunt volumes.DiscussionWe suggest that PFO may be associated with the development of two distinct cerebrovascular conditions (stroke and "silent" WM lesions), each characterized by unique imaging patterns. Further studies are needed to identify better the "at-risk" PFOs and gain deeper insights into their clinical implications.
| S-EPMC10909929 | biostudies-literature
Project description:Cerebrovascular diseases are conditions caused by problems with brain vasculature, which have a high morbidity and mortality. Aquaporin-4 (AQP4) is the most abundant water channel in the brain and crucial for the formation and resolution of brain edema. Considering brain edema is an important pathophysiological change after stoke, AQP4 is destined to have close relation with cerebrovascular diseases. However, this relation is not limited to brain edema due to other biological effects elicited by AQP4. Till now, multiple studies have investigated roles of AQP4 in cerebrovascular diseases. This review focuses on expression of AQP4 and the effects of AQP4 on brain edema and neural cells injuries in cerebrovascular diseases including cerebral ischemia, intracerebral hemorrhage and subarachnoid hemorrhage. In the current review, we pay more attention to the studies of recent years directly from cerebrovascular diseases animal models or patients, especially those using AQP4 gene knockout mice. This review also elucidates the potential of AQP4as an excellent therapeutic target.
| S-EPMC5000647 | biostudies-other
Project description:CRISPR/Cas9 genome editing can facilitate efficient deletion of genomic region, but it has not been used to delete an entire chromosome. Here, Adikusuma et al. show proof-of-concept for efficient CRISPR-mediated selective chromosome deletion by removing the centromere or shredding the chromosome arm in mouse embryonic stem cells and zygotes.
| S-EPMC5542798 | biostudies-literature
Project description:BackgroundPost-stroke immune depression contributes to the development of infections which are major complications after stroke. Previous experimental and clinical studies suggested that humoral stress mediators induce immune dysfunction. However, prospective clinical studies testing this concept are missing and no data exists for other cerebrovascular diseases including intracerebral hemorrhage (ICH) and TIA.MethodsWe performed a prospective clinical study investigating 166 patients with TIA, ischemic and hemorrhagic stroke. We measured a broad panel of stress mediators, leukocyte subpopulations, cytokines and infection markers from hospital admission to day 7 and on follow-up after 2-3 months. Multivariate regression analyses detected independent predictors of immune dysfunction and bacterial infections. ROC curves were used to test the diagnostic value of these parameters.ResultsOnly severe ischemic strokes and ICH increased some catecholamine metabolites, ACTH and cortisol levels. Immunodysfunction was eminent already on hospital admission after large brain lesions with lymphocytopenia as a key feature. None of the stress mediators was an independent predictor of lymphocytopenia or infections. However, lymphocytopenia on hospital admission was detected as an independent explanatory variable of later infections. NIHSSS and lymphocytopenia on admission were excellent predictors of infection.ConclusionsOur results question the present pathophysiological concept of stress-hormone mediated immunodysfunction after stroke. Early lymphocytopenia was identified as an early independent predictor of post-stroke infections. Absence of lymphocytopenia may serve as a negative predictive marker for stratification for early antibiotic treatment.
| S-EPMC3777986 | biostudies-literature
Project description:PurposeComplete interferon-γ receptor 1 (IFN-γR1) deficiency is a primary immunodeficiency causing predisposition to severe infection due to intracellular pathogens. Only 36 cases have been reported worldwide. The purpose of this article is to describe a large novel deletion found in 3 related cases, which resulted in the complete removal of the IFNGR1 gene.MethodsWhole blood from three patients was stimulated with lipopolysaccharide (LPS) and IFN-γ to determine production of tumor necrosis factor (TNF), interleukin-12 p40 (IL-12p40) and IL-10. Expression of IFN-γR1 on the cell membrane of patients' monocytes was assessed using flow cytometry. IFNGR1 transcript was analyzed in RNA and the gene and adjacent regions were analyzed in DNA. Finally, IL22RA2 transcript levels were analyzed in whole blood cells and dendritic cells.ResultsThere was no expression of the IFN-γR1 on the monocytes. Consistent with this finding, there was no IFN-γ response in the whole blood assay as measured by effect on LPS-induced IL-12p40, TNF and IL-10 production. A 119.227 nt homozygous deletion on chromosome 6q23.3 was identified, removing the IFNGR1 gene completely and ending 117 nt upstream of the transcription start of the IL22RA2 gene. Transcript levels of IL22RA2 were similar in patient and control.ConclusionsWe identified the first large genomic deletion of IFNGR1 causing complete IFN-γR1 deficiency. Despite the deletion ending very close to the IL22RA2 gene, it does not appear to affect IL22RA2 transcription and, therefore, may not have any additional clinical consequence.
| S-EPMC4792359 | biostudies-literature
Project description:Cerebrovascular diseases are one of the leading causes of death worldwide, however, little progress has been made in preventing or treating these diseases to date. The transforming growth factor-? (TGF-?) signaling pathway plays crucial and highly complicated roles in cerebrovascular development and homeostasis, and dysregulated TGF-? signaling contributes to cerebrovascular diseases. In this review, we provide an updated overview of the functional role of TGF-? signaling in the cerebrovascular system under physiological and pathological conditions. We discuss the current understanding of TGF-? signaling in cerebral angiogenesis and the maintenance of brain vessel homeostasis. We also review the mechanisms by which disruption of TGF-? signaling triggers or promotes the progression of cerebrovascular diseases. Finally, we briefly discuss the potential of targeting TGF-? signaling to treat cerebrovascular diseases.
| S-EPMC7530326 | biostudies-literature
Project description:Pericytes are functional components of the neurovascular unit (NVU) that are located around the blood vessels, and their roles in the regulation of cerebral health and diseases has been reported. Currently, the potential properties of pericytes as emerging therapeutic targets for cerebrovascular diseases have attracted considerable attention. Nonetheless, few reviews have comprehensively discussed pericytes and their roles in cerebrovascular diseases. Therefore, in this review, we not only summarized and described the basic characteristics of pericytes but also focused on clarifying the new understanding about the roles of pericytes in the pathogenesis of cerebrovascular diseases, including white matter injury (WMI), hypoxic-ischemic brain damage, depression, neovascular insufficiency disease, and Alzheimer's disease (AD). Furthermore, we summarized the current therapeutic strategies targeting pericytes for cerebrovascular diseases. Collectively, this review is aimed at providing a comprehensive understanding of pericytes and new insights about the use of pericytes as novel therapeutic targets for cerebrovascular diseases.
| S-EPMC6882740 | biostudies-literature
Project description:Cellular aging is the most severe risk factor for neurodegenerative disease. Simultaneously, oxidative stress (OS) is a critical factor in the aging process, resulting from an imbalance between reactive oxygen and nitrogen species and the antioxidant defense system. Emerging evidence indicates that OS is a common cause of several age-related brain pathologies, including cerebrovascular diseases. Elevated OS disrupts endothelial functional ability by diminishing the bioavailability of nitric oxide (a vascular dilator), induces atherosclerosis, and impairs vasculature, which are all common characteristics of cerebrovascular disease. In this review, we summarize evidence supporting an active role of OS in cerebrovascular disease progression, focusing primarily on stroke pathogenesis. We briefly discuss hypertension, diabetes, heart disease, and genetic factors that are often linked to OS and are considered associated factors influencing stroke pathology. Finally, we discuss the current pharmaceutics/therapeutics available for treating several cerebrovascular diseases.
| S-EPMC9982100 | biostudies-literature
Project description:Sotos syndrome is an overgrowth syndrome characterized by distinctive facial features and intellectual disability caused by haploinsufficiency of the NSD1 gene. Genotype-phenotype correlations have been observed, with major anomalies seen more frequently in patients with 5q35 deletions than those with point mutations in NSD1. Though endocrine features have rarely been described, transient hyperinsulinemic hypoglycemia (HI) of the neonatal period has been reported as an uncommon presentation of Sotos syndrome. Eight cases of 5q35 deletions and one patient with an intragenic NSD1 mutation with transient HI have been reported. Here, we describe seven individuals with HI caused by NSD1 gene mutations with three having persistent hyperinsulinemic hypoglycemia. These patients with persistent HI and Sotos syndrome caused by NSD1 mutations, further dispel the hypothesis that HI is due to the deletion of other genes in the deleted 5q35 region. These patients emphasize that NSD1 haploinsufficiency is sufficient to cause HI, and suggest that Sotos syndrome should be considered in patients presenting with neonatal HI. Lastly, these patients help extend the phenotypic spectrum of Sotos syndrome to include HI as a significant feature.
| S-EPMC6454923 | biostudies-literature
Project description:Background The causal relationship between gut microbiota and cerebrovascular disease remains unknown, despite several recent studies reporting an association between the two. Methods To assess this relationship, we conducted a two-sample Mendelian randomization (MR) using summary statistics data from published genome-wide association studies (GWAS). This analysis allowed us to identify bacterial taxa that may affect cerebrovascular disease. Furthermore, we performed reverse MR to further analyze the significant bacterial taxa. Finally, we conducted a two-step MR analysis to examine the mediating role of metabolic factors [systolic blood pressure (SBP), type 2 diabetes (T2D), and body mass index (BMI)] in the association between gut microbiota and cerebrovascular disease. Additionally, a series of sensitivity analyses were carried out to validate the robustness of our findings. Results Our results showed that a genetically predicted high abundance of family Porphyromonadaceae reduced the risk of intracranial aneurysms (IA). Moreover, using inverse variance weighted (IVW) estimates, we found a nominal causal relationship between seventeen gut microbiota and IA, as well as its subtypes. In the case of stroke and its subtypes, we observed a nominal causal relationship with thirteen, eleven, eleven, nine, and eight bacteria for AS, AIS, CES, LAS, and SVS, respectively. Reverse MR analysis showed no significant causal relationship between intracranial aneurysms and gut microbiota. However, we did find that genetically predicted any stroke (AS) and any ischemic stroke (AIS) reduced the abundance of family Clostridiaceae1 (OR: 0.74, 95% CI: 0.62–0.87, p = 3.39 × 10−4, and OR: 0.75, 95% CI: 0.66–0.87, p = 7.06 × 10−5, respectively). Furthermore, genetic prediction of AIS (OR: 0.87, 95% CI: 0.77–0.99, p = 3.05 × 10−2) was associated with a reduced abundance of the order Clostridiales. Moreover, genus Streptococcus exhibited effects on AS, AIS, and SVS which were mediated by T2D. Conversely, the association between genus Eubacterium brachy group and AIS was mediated by SBP. No significant heterogeneity of instrumental variables or horizontal pleiotropy was observed. Conclusion This MR analysis indicates that there exists a beneficial or detrimental causal effect of gut microbiota composition on cerebrovascular disease. And SBP and T2D may play mediating role in this process.
| S-EPMC10448814 | biostudies-literature