A Novel Frameshift Mutation in the ITGB3 Gene Leading to Glanzmann’s Thrombasthenia in a Saudi Arabian Family

Alharbi, Ahmed Eid; Hashmi, Jamil Amjad; Alharby, Essa; Albalawi, Alia M.; Ramzan, Khushnooda; Basit, Sulman

doi:10.1016/j.hemonc.2021.01.003

Cited by 4 publications

(5 citation statements)

References 31 publications

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“…In addition, fibrinogen receptor α IIb β 3, which is an integrin, is formed by the two proteins [ 46 ]. Integrin α IIb β 3 is a heterodimeric receptor abundantly expressed in platelet plasma membranes, and its activation and binding to soluble ligands (mainly fibrinogen, as well as vWF and fibronectin) are required for platelet activation, adhesion, and aggregation [ 38 , 47 , 48 ]. The α IIb β 3 integrin has a modest affinity for ligands in resting platelets [ 49 – 51 ].…”

Section: Discussionmentioning

confidence: 99%

Weighted Gene Co-Expression Network Analysis to Identify Potential Biological Processes and Key Genes in COVID-19-Related Stroke

Cen

Liu

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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The purpose of this research was to explore the underlying biological processes causing coronavirus disease 2019- (COVID-19-) related stroke. The Gene Expression Omnibus (GEO) database was utilized to obtain four COVID-19 datasets and two stroke datasets. Thereafter, we identified key modules via weighted gene co-expression network analysis, following which COVID-19- and stroke-related crucial modules were crossed to identify the common genes of COVID-19-related stroke. The common genes were intersected with the stroke-related hub genes screened via Cytoscape software to discover the critical genes associated with COVID-19-related stroke. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for common genes associated with COVID-19-related stroke, and the Reactome database was used to annotate and visualize the pathways involved in the key genes. Two COVID-19-related crucial modules and one stroke-related crucial module were identified. Subsequently, the top five genes were screened as hub genes after visualizing the genes of stroke-related critical module using Cytoscape. By intersecting the COVID-19- and stroke-related crucial modules, 28 common genes for COVID-19-related stroke were identified. ITGA2B and ITGB3 have been further identified as crucial genes of COVID-19-related stroke. Functional enrichment analysis indicated that both ITGA2B and ITGB3 were involved in integrin signaling and the response to elevated platelet cytosolic Ca2+, thus regulating platelet activation, extracellular matrix- (ECM-) receptor interaction, the PI3K-Akt signaling pathway, and hematopoietic cell lineage. Therefore, platelet activation, ECM-receptor interaction, PI3K-Akt signaling pathway, and hematopoietic cell lineage may represent the potential biological processes associated with COVID-19-related stroke, and ITGA2B and ITGB3 may be potential intervention targets for COVID-19-related stroke.

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Section: Discussionmentioning

confidence: 99%

Weighted Gene Co-Expression Network Analysis to Identify Potential Biological Processes and Key Genes in COVID-19-Related Stroke

Cen

Liu

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…GT is a rare inherited abnormal platelet function disorder ( 12 , 13 ). Patients with GT may experience mild to severe bleeding symptoms, including easy bruising, epistaxis, mucosal bleeding, and increased bleeding after trauma or surgery ( 14 , 15 ).…”

Section: Discussionmentioning

confidence: 99%

Novel homozygous silent mutation of ITGB3 gene caused Glanzmann thrombasthenia

Wang

Sun

et al. 2023

Front. Pediatr.

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Glanzmann thrombasthenia (GT) is a rare inherited disease characterized by mucocutaneous bleeding due to the abnormalities in quantity or quality of platelet membrane GP IIb (CD41) or GP IIIa (CD61). GP IIb and GP IIIa are encoded by the ITGA2B and ITGB3 genes, respectively. Herein, we described a 7-year-old Chinese boy of the consanguineous couple who was diagnosed with GT based on the typical clinical manifestations, absence of blood clot retraction and the reduced expression of CD41 and CD61 in platelets. A homozygous silent variant c.1431C > T (p. G477=) of the ITGB3 gene was identified by the Whole-exome sequencing and confirmed by Sanger sequencing. The variant was predicted to affect the splicing. RT-PCR and sequencing revealed that the variant caused a deletion of 95 base pairs and frameshift, and subsequently created a premature stop codon in exon 10 of ITGB3 (p. G477Afs*30). It was indicated that the variant c.1431C > T (p. G477=) of ITGB3 was the cause for Glanzmann thrombasthenia. Our findings expanded the mutation spectrum and provided the information for the genetic counseling, prenatal diagnosis and preimplantation genetic testing (PGT).

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“…Integrin β3 was found with αIIβ chains in platelets. Integrins are involved in cell adhesion and cell surface-mediated signal transduction (Alharbi et al 2021). Overall, loss of ITGB3, which encodes integrin β3, exacerbates atherosclerosis in high-fat diet-fed ApoE (−/−) mice (Weng et al 2003;Misra et al 2018).…”

Section: Discussionmentioning

confidence: 99%

miR-351 promotes atherosclerosis in diabetes by inhibiting the ITGB3/PIK3R1/Akt pathway and induces endothelial cell injury and lipid accumulation

Song

Liu

et al. 2022

Mol Med

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Background The miR-351 gene is significantly upregulated in diabetic mice with atherosclerosis. However, the mechanism by which its presence is important for the overall disease has not been elucidated. Therefore, this study will investigate the mechanism of miR-351 in the process of diabetes mellitus with atherosclerosis through miR-351 gene knockout mice. Methods In this study, miR-351−/− C57BL/6 mice were first induced to form a type 2 diabetes mellitus model with atherosclerosis by STZ injection and a high-fat diet. Pathological tests (oil red O, HE, and Masson staining) combined with biochemical indices (TC, TG, LDL-C, HDL-C, TNF-α, hs-CRP, NO, SOD, MDA, CAT, and GSH-Px) were performed to evaluate the pathological degree of atherosclerosis in each group. Mouse aortic endothelial cells were treated with oxidized low-density lipoprotein (ox-LDL) and 30 mM glucose to establish a diabetic atherosclerosis cell model. Combined with cell oil red O staining and flow cytometry, the effects of silencing miR-351 on lipid accumulation and cell apoptosis in the diabetic atherosclerosis cell model were determined. Fluorescence in situ hybridization was used to detect the localization and transcription levels of miR-351 in cells. The target genes of miR-351 were predicted by bioinformatics and verified by dual-luciferase activity reporting. Western blotting was used to detect the expression levels of phosphorylated inosine 3-kinase regulatory subunit 1 (PIK3R1)/serine/threonine kinase 1 (Akt) and apoptosis-related proteins after transfection with integrin subunit β3 (ITGB3) small interfering ribonucleic acid (siRNA). Results The expression of the miR-351 gene was significantly increased in the high-fat wild-type (HWT) group, and its expression was significantly decreased in the knockout mice. Silencing miR-351 effectively alleviated atherosclerosis in mice. The levels of miR-351 expression, apoptosis, lipid accumulation, and oxidative stress in ox-LDL + high glucose-induced endothelial cells were significantly increased. These phenomena were effectively inhibited in lentivirus-infected miR-351-silenced cell lines. Bioinformatics predicted that miR-351-5p could directly target the ITGB3 gene. Transfection of ITGB3 siRNA reversed the downregulation of apoptosis, decreased oil accumulation, and decreased oxidative stress levels induced by miR-351 silencing. In addition, it inhibited the activation of the PIK3R1/Akt pathway. Conclusion Silencing miR-351 upregulates ITGB3 and activates the PIK3R1/Akt pathway, thereby exerting anti-apoptosis and protective effects on endothelial cells.

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A Novel Frameshift Mutation in the ITGB3 Gene Leading to Glanzmann’s Thrombasthenia in a Saudi Arabian Family

Cited by 4 publications

References 31 publications

Weighted Gene Co-Expression Network Analysis to Identify Potential Biological Processes and Key Genes in COVID-19-Related Stroke

Weighted Gene Co-Expression Network Analysis to Identify Potential Biological Processes and Key Genes in COVID-19-Related Stroke

Novel homozygous silent mutation of ITGB3 gene caused Glanzmann thrombasthenia

miR-351 promotes atherosclerosis in diabetes by inhibiting the ITGB3/PIK3R1/Akt pathway and induces endothelial cell injury and lipid accumulation

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