Chronic Granulomatous Disease and Myelodysplastic Syndrome in a Patient with a Novel Mutation in CYBB

Reis, Bárbara C. S.; Cunha, Daniela P.; Bueno, Ana Paula Silva; Carvalho, Flavia Amendola Anisio de; Dutra, Juliana Teixeira; Mello, Fabiana V.; Ribeiro, Maria Cecília Menks; Milito, Cristiane; Costa, Elaine Sobral da; Vasconcelos, Zilton

doi:10.3390/genes12101476

Cited by 3 publications

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“…It’s thought to be a vital component of the phagocyte’s microbicidal oxidase system. One of five biochemical deficiencies linked to chronic granulomatous illness has been identified: CYBB deficiency (CGD) [ 61 ]. The activity of phagocyte NADPH oxidase is reduced in this disease, which allows neutrophils to phagocytize germs but not destroy them in the phagocytic vacuoles.…”

Section: Discussionmentioning

confidence: 99%

Entamoeba histolytica HM-1: IMSS gene expression profiling identifies key hub genes, potential biomarkers, and pathways in Amoebiasis infection: a systematic network meta-analysis

et al. 2022

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Entamoeba histolytica (E. histolytica) is an anaerobic parasite that causes Amoebiasis in the intestine or extraintestinal, with immunology, genetics, and environmental variables all playing a part in the disease's development, but its molecular mechanism is unknown. One of the primary obstacles in understanding the etiology of Amoebiasis will be identifying the genetics profiling that controls the amoebiasis network. By examining the gene expression profile of Amoebiasis and comparing it to healthy controls, we were able to identify differentially expressed genes (DEGs). Differentially expressed genes were used to build the amoebiasis protein interaction network and calculated its network topological properties. We discovered that nine key hub genes(KHGs) are JUN, PTGS2, FCGR3A, MNDA, CYBB, EGR1, CCL2, TLR8, and LRRK2 genes. The genes JUN and EGR1 were transcriptional factors (TFs) and up-regulated, others down-regulated. hsa-miR-155-5p,hsa-miR-101-3p,hsa-miR-124-3p,hsa-miR-26b-5p and hsa-miR-16-5p are also among the essential miRNAs that have been demonstrated to be targeted by key hub genes. These KHGs were primarily enriched in the IL-17 signaling pathway, TNF signaling pathway, NOD-like receptor signaling pathway, Toll-like receptor signaling pathway. miRNAs were grouped in various pathways, focusing on the TGF−beta signaling pathway, Human immunodeficiency virus 1 infection, Insulin signaling pathway, Signaling pathways regulating pluripotency of stem cells, etc. Amoebiasis KHGs (JUN, PTGS2, CCL2, MNDA) and their associated miRNAs are the primary targets for therapeutic methods and possible biomarkers. Furthermore, we identified drugs for genes JUN, PTGS2, FCGR3A, CCL2, and LRRK2. KHGs, on the other hand, required experimental validation to prove their efficacy.

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Section: Discussionmentioning

confidence: 99%

Entamoeba histolytica HM-1: IMSS gene expression profiling identifies key hub genes, potential biomarkers, and pathways in Amoebiasis infection: a systematic network meta-analysis

et al. 2022

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Reconstructed glycosylase base editors GBE2.0 with enhanced C-to-G base editing efficiency and purity

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et al. 2022

Molecular Therapy

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Genetic screening in a Brazilian cohort with inborn errors of immunity

Ferreira,

Francisco Junior,

Gerber

et al. 2023

BMC Genom Data

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Background Inherited genetic defects in immune system-related genes can result in Inborn Errors of Immunity (IEI), also known as Primary Immunodeficiencies (PID). Diagnosis of IEI disorders is challenging due to overlapping clinical manifestations. Accurate identification of disease-causing germline variants is crucial for appropriate treatment, prognosis, and genetic counseling. However, genetic sequencing is challenging in low-income countries like Brazil. This study aimed to perform genetic screening on patients treated within Brazil's public Unified Health System to identify candidate genetic variants associated with the patient’s phenotype. Methods Thirteen singleton unrelated patients from three hospitals in Rio de Janeiro were enrolled in this study. Genomic DNA was extracted from the peripheral blood lymphocytes of each patient, and whole exome sequencing (WES) analyses were conducted using Illumina NextSeq. Germline genetic variants in IEI-related genes were prioritized using a computational framework considering their molecular consequence in coding regions; minor allele frequency ≤ 0.01; pathogenicity classification based on American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines gathered from the VarSome clinical database; and IEI-related phenotype using the Franklin tool. The genes classification into IEI categories follows internationally recognized guidelines informed by the International Union of Immunological Societies Expert Committee. Additional methods for confirmation of the variant included Sanger sequencing, phasing analysis, and splice site prediction. Results A total of 16 disease-causing variants in nine genes, encompassing six different IEI categories, were identified. X-Linked Agammaglobulinemia, caused by BTK variations, emerged as the most prevalent IEI disorder in the cohort. However, pathogenic and likely pathogenic variants were also reported in other known IEI-related genes, namely CD40LG, CARD11, WAS, CYBB, C6, and LRBA. Interestingly, two patients with suspected IEI exhibited pathogenic variants in non-IEI-related genes, ABCA12 and SLC25A13, potentially explaining their phenotypes. Conclusions Genetic screening through WES enabled the detection of potentially harmful variants associated with IEI disorders. These findings contribute to a better understanding of patients' clinical manifestations by elucidating the genetic basis underlying their phenotypes.

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Chronic Granulomatous Disease and Myelodysplastic Syndrome in a Patient with a Novel Mutation in CYBB

Cited by 3 publications

References 15 publications

Entamoeba histolytica HM-1: IMSS gene expression profiling identifies key hub genes, potential biomarkers, and pathways in Amoebiasis infection: a systematic network meta-analysis

Entamoeba histolytica HM-1: IMSS gene expression profiling identifies key hub genes, potential biomarkers, and pathways in Amoebiasis infection: a systematic network meta-analysis

Reconstructed glycosylase base editors GBE2.0 with enhanced C-to-G base editing efficiency and purity

Genetic screening in a Brazilian cohort with inborn errors of immunity

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