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Medicine Jun 2024With advances in prenatal diagnostic techniques, chromosomal microdeletions and microduplications have become the focus of prenatal diagnosis. 7q partial monosomy or... (Review)
Review
RATIONALE
With advances in prenatal diagnostic techniques, chromosomal microdeletions and microduplications have become the focus of prenatal diagnosis. 7q partial monosomy or trisomy due to a deletion or duplication of the 7q end is relatively rare and usually originates from parents carrying a balanced translocation.
PATIENT CONCERNS
Noninvasive prenatal screening (NIPT) showed a fetus with partial deletion and duplication of chromosome 7q. It was not possible to determine whether the fetus was normal.
DIAGNOSES
Conventional chromosome G-banding and chromosome microarray analysis (CMA) were performed on fetal amniotic fluid samples and parental peripheral blood samples.
INTERVENTIONS
The pregnant women were given detailed genetic counseling by clinicians.
OUTCOMES
The fetal karyotype was 46, XY on conventional G-banding analysis. The CMA test results showed a deletion of approximately 7.8 Mb in the 7q36.1q36.3 region and a duplication of 6.6Mb in the 7q35q36.1 region. The parents' karyotype analysis and CMA results were normal, indicating a new mutation.
LESSONS
CMA molecular diagnostic analysis can effectively detect chromosomal microdeletions or microduplications, clarify the relationship between fetal genotype and clinical phenotype, and provide a reference for prenatal diagnosis of chromosomal microdeletion-duplication syndrome.
Topics: Humans; Female; Chromosomes, Human, Pair 7; Pregnancy; Chromosome Deletion; Adult; Chromosome Duplication; Prenatal Diagnosis; Noninvasive Prenatal Testing; Chromosome Banding; Karyotyping; Microarray Analysis
PubMed: 38847723
DOI: 10.1097/MD.0000000000038461 -
Annals of Medicine and Surgery (2012) Jun 2024Burkitt lymphoma (BL) is an aggressive non-Hodgkin lymphoma characterized by chromosome 8 MYC gene translocation. It manifests in three clinical types:...
INTRODUCTION
Burkitt lymphoma (BL) is an aggressive non-Hodgkin lymphoma characterized by chromosome 8 MYC gene translocation. It manifests in three clinical types: immunodeficiency-related, sporadic (nonendemic), and endemic (African), each differing in epidemiology and clinical behavior. Treatment typically involves enrollment in clinical trials or intensive chemotherapy regimens like R-CODOX-M/IVAC. The authors present a case of recurrent BL following treatment.
CASE REPORT
A 13-year-old female presented with a gradually progressive swelling in the left parieto-occipital region. Examination revealed normal vital signs and a Glasgow coma scale, with seronegative findings on investigations. An excision of a subganglion soft tissue tumor was performed, revealing histopathological features suggestive of a small round blue cell tumor. After chemotherapy, the patient experienced a recurrence in the scalp region, diagnosed as BL.
DISCUSSION
While scarce reports exist on BL in the scalp region, cases have been documented in various body locations. Treatment strategies, including chemotherapy and surgery, have shown promising results in managing the disease and improving symptoms.
CONCLUSION
The recurrence of BL is rare, highlighting the importance of vigilance in monitoring patients post-treatment. The authors report a case of recurrent BL in a 13-year-old female, emphasizing the need for continued research and surveillance in managing this aggressive malignancy.
PubMed: 38846844
DOI: 10.1097/MS9.0000000000002089 -
Scientific Reports Jun 2024The inhibition of tumor necrosis factor (TNF)-α trimer formation renders it inactive for binding to its receptors, thus mitigating the vicious cycle of inflammation. We...
The inhibition of tumor necrosis factor (TNF)-α trimer formation renders it inactive for binding to its receptors, thus mitigating the vicious cycle of inflammation. We designed a peptide (PIYLGGVFQ) that simulates a sequence strand of human TNFα monomer using a series of in silico methods, such as active site finding (Acsite), protein-protein interaction (PPI), docking studies (GOLD and Flex-X) followed by molecular dynamics (MD) simulation studies. The MD studies confirmed the intermolecular interaction of the peptide with the TNFα. Fluorescence-activated cell sorting and fluorescence microscopy revealed that the peptide effectively inhibited the binding of TNF to the cell surface receptors. The cell culture assays showed that the peptide significantly inhibited the TNFα-mediated cell death. In addition, the nuclear translocation of the nuclear factor kappa B (NFκB) was significantly suppressed in the peptide-treated A549 cells, as observed in immunofluorescence and gel mobility-shift assays. Furthermore, the peptide protected against joint damage in the collagen-induced arthritis (CIA) mouse model, as revealed in the micro focal-CT scans. In conclusion, this TNFα antagonist would be helpful for the prevention and repair of inflammatory bone destruction and subsequent loss in the mouse model of CIA as well as human rheumatoid arthritis (RA) patients. This calls upon further clinical investigation to utilize its potential effect as an antiarthritic drug.
Topics: Humans; Tumor Necrosis Factor-alpha; Animals; Mice; Peptides; Arthritis, Experimental; Molecular Docking Simulation; A549 Cells; Molecular Dynamics Simulation; NF-kappa B; Male; Antirheumatic Agents; Protein Binding; Disease Models, Animal
PubMed: 38839973
DOI: 10.1038/s41598-024-63790-6 -
Kidney Diseases (Basel, Switzerland) Jun 2024G protein-coupled bile acid receptor (TGR5), the first G protein-coupled receptor for bile acids identified, is capable of activating a variety of intracellular...
INTRODUCTION
G protein-coupled bile acid receptor (TGR5), the first G protein-coupled receptor for bile acids identified, is capable of activating a variety of intracellular signaling pathways after interacting with bile acids. TGR5 plays an important role in multiple physiological processes and is considered to be a potential target for the treatment of various metabolic diseases, including type 2 diabetes. Evidence has emerged that genetic deletion of TGR5 results in an increase in basal urine output, suggesting that it may play a critical role in renal water and salt reabsorption. The present study aims to elucidate the effect and mechanism of TGR5 activation on urine concentration.
METHODS
Mice were treated with TGR5 agonists (LCA and INT-777) for 3 days. The 24-h urine of mice was collected and analyzed for urine biochemical parameters. The mRNA expressions were detected by real-time PCR, and the protein expressions were detected by western blot. Immunohistochemistry and immunofluorescence were performed to examine the cellular location of proteins. The cultured primary medullary collecting duct cells were pretreated with H89 (a PKA inhibitor) for 1 h, followed by 12-h treatment of LCA and INT-777. Luciferase reporter assays were used to detect the effect of CREB on the gene transcription of AQPs. Gel electrophoretic mobility shift assays were used to analyze DNA-protein interactions.
RESULTS
Treatment of mice with the TGR5 agonist LCA and INT-777 markedly reduced urine output and increased urine osmolality, accompanied by a marked increase in AQP2 and AQP3 protein expression and membrane translocation. In cultured primary medullary collecting duct cells, LCA and INT-777 dose-dependently upregulated AQP2 and AQP3 expression in a cAMP/PKA-dependent manner. Mechanistically, both AQP2 and AQP3 gene promoter contains a putative CREB-binding site, which can be bound and activated by CREB as assessed by both gene promoter-driven luciferase and gel shift assays.
CONCLUSION
Collectively, our findings demonstrate that activation of TGR5 can promote urine concentration by upregulation of AQP2 and AQP3 expression in renal collecting ducts. TGR5 may represent an attractive target for the treatment of patients with urine concentration defect.
PubMed: 38835402
DOI: 10.1159/000538107 -
Scientific Reports Jun 2024Previous studies showed that Australian wheat cultivars Janz and Sunco carry leaf rust and stem rust resistance genes Lr24 and Sr24 derived from Thinopyrum ponticum...
Previous studies showed that Australian wheat cultivars Janz and Sunco carry leaf rust and stem rust resistance genes Lr24 and Sr24 derived from Thinopyrum ponticum chromosome arm 3AgL. However, the size of the alien segments carrying Lr24 and Sr24 in the lines were not determined. In this study, we used non-denaturing fluorescence in situ hybridization (ND-FISH), genomic in situ hybridization (GISH), and PCR-based landmark unique gene (PLUG) markers to visualize the alien segments in Janz and Sunco, and further compared them with the segments in US cultivars Agent and Amigo. The fraction length (FL) of the alien translocation in Agent was 0.70-1.00, whereas those in Janz, Sunco, and Amigo were smaller, at FL 0.85-1.00. It was deduced that the alien gene R encoding for red grain color and rust resistance genes Lr24 and Sr24 on chromosome arm 3AgL were in bins of FL 0.70-0.85 and 0.85-1.00, respectively. We retrieved and extracted nucleotide-binding site-leucine-rich repeat (NBS-LRR) receptor genes corresponding to the region of Lr24 and Sr24 on chromosomes 3E, and 3J, 3J and 3St from the reference genome sequences of Th. elongatum and Th. intermedium, respectively. A set of molecular markers developed for Lr24 and Sr24 from those extracted NBS-LRR genes will provide valuable information for fine mapping and cloning of these genes.
Topics: Triticum; Disease Resistance; Plant Diseases; Chromosomes, Plant; Genes, Plant; In Situ Hybridization, Fluorescence; Basidiomycota; Chromosome Mapping
PubMed: 38834653
DOI: 10.1038/s41598-024-63835-w -
MBio Jun 2024expresses a type IV protein secretion system (T4SS) that promotes contact-dependent killing of other bacteria and does so partly by secreting the effector TfcB. Here,...
expresses a type IV protein secretion system (T4SS) that promotes contact-dependent killing of other bacteria and does so partly by secreting the effector TfcB. Here, we report the structure of TfcB, comprising an N-terminal domain similar to the catalytic domain of glycosyl hydrolase (GH-19) chitinases and a C-terminal domain for recognition and translocation by the T4SS. Utilizing a two-hybrid assay to measure effector interactions with the T4SS coupling protein VirD4, we documented the existence of five more T4SS substrates. One of these was protein 20845, an annotated nuclease. A mutant lacking the gene for 20845 was impaired for killing , , and . Moreover, the cloned 20845 gene conferred robust toxicity, with the recombinant being rescued when 20845 was co-expressed with its cognate immunity protein. The 20845 effector was an 899 amino-acid protein, comprised of a GHH-nuclease domain in its N-terminus, a large central region of indeterminant function, and a C-terminus for secretion. Engineered variants of the 20845 gene that had mutations in the predicted catalytic site did not impede , indicating that the antibacterial effect of 20845 involves its nuclease activity. Using flow cytometry with DNA staining, we determined that 20845, but not its mutant variants, confers a loss in DNA content of target bacteria. Database searches revealed that uncharacterized homologs of 20845 occur within a range of bacteria. These data indicate that the T4SS promotes interbacterial competition through the action of multiple toxic effectors, including a potent, novel DNase.IMPORTANCE is a multi-drug-resistant, Gram-negative bacterium that is an emerging pathogen of humans. Patients with cystic fibrosis are particularly susceptible to infection. In hospital water systems and various types of infections, co-exists with other bacteria, including other pathogens such as . We previously demonstrated that has a functional VirB/D4 type VI protein secretion system (T4SS) that promotes contact-dependent killing of other bacteria. Since most work on antibacterial systems involves the type VI secretion system, this observation remains noteworthy. Moreover, currently stands alone as a model for a human pathogen expressing an antibacterial T4SS. Using biochemical, genetic, and cell biological approaches, we now report both the discovery of a novel antibacterial nuclease (TfdA) and the first structural determination of a bactericidal T4SS effector (TfcB).
PubMed: 38832773
DOI: 10.1128/mbio.01198-24 -
The Application of Clinical Genetics 2024Optical Genome Mapping (OGM) technology has garnered growing interest for the identification of chromosomal structural variations (SVs), particularly complex ones that...
Optical Genome Mapping Identifies a Novel Unbalanced Translocation Between Chromosomes 4q and 6q Leading to Feeding Difficulties and Hypotonia in a Neonate: A Case Report.
Optical Genome Mapping (OGM) technology has garnered growing interest for the identification of chromosomal structural variations (SVs), particularly complex ones that are implicated in genetic diseases in humans. In this study, we performed genetic diagnostics on a neonatal patient who presented with feeding difficulties, hypotonia, and an atrial septal defect. We utilized a combination of trio-whole exome sequencing and OGM for our analysis. The results revealed an unbalanced translocation between maternal chromosomes 4 and 6 in the proband, ogm[GRch38]t(4:6)(q35.2;q25.3), resulting in a 2.8 Mb deletion at the 4q35 terminal and a 10.2 Mb duplication at the 6q25 terminal. In summary, this study highlights how OGM, in conjunction with other genetic approaches, can unveil the genetic etiology of complex clinical syndromes. Neonatal patients often exhibit low specific phenotypes, underlining the significance of SV detection.
PubMed: 38828444
DOI: 10.2147/TACG.S465244 -
Diabetes, Metabolic Syndrome and... 2024Recent studies suggest gut-derived lipopolysaccharide (LPS)-translocation to play a role in both systemic inflammation and in inflammatory adipose tissue. We aimed to...
BACKGROUND
Recent studies suggest gut-derived lipopolysaccharide (LPS)-translocation to play a role in both systemic inflammation and in inflammatory adipose tissue. We aimed to investigate whether circulating LPS-related inflammatory markers and corresponding genetic expression in adipose tissue were associated with obesity, cardiometabolic risk factors, and dietary habits in patients with coronary artery disease.
METHODS
Patients (n=382) suffering a myocardial infarction 2-8 weeks prior to inclusion were enrolled in this cross-sectional study. Subcutaneous adipose tissue (SAT), taken from the gluteal region, and fasting blood samples were collected at inclusion for determination of genetic expression of LPS-binding protein (LBP), CD14, toll-like receptor 2 (TLR2), and TLR4 in SAT, and LPS, LBP, and soluble cluster of differentiation 14 (sCD14) in the circulation. All patients filled out a dietary registration form.
RESULTS
Patients (median age 74 years, 25% women), had a median body mass index (BMI) of 25.9 kg/m. Circulating levels of LBP correlated to BMI (=0.02), were significantly higher in overweight or obese (BMI≥25 kg/m) compared to normal- or underweight patients (BMI<25 kg/m), and were significantly elevated in patients with T2DM, hypertension, and MetS, compared to patients without (≤0.04, all). In SAT, gene expression of CD14 and LBP correlated significantly to BMI (≤0.001, both), and CD14 and TLR2 expressions were significantly higher in patients with T2DM and MetS compared to patients without (≤0.001, both). Circulating and genetically expressed CD14 associated with use of n-3 PUFAs (=0.008 and =0.003, respectively). No other significant associations were found between the measured markers and dietary habits.
CONCLUSION
In patients with established CAD, circulating levels of LBP and gene expression of CD14 and TLR2 in SAT were related to obesity, MetS, T2DM, and hypertension. This suggests that the LPS-LBP-CD14 inflammatory axis is activated in the chronic low-grade inflammation associated with cardiometabolic abnormalities, whereas no significant associations with dietary habits were observed.
PubMed: 38827167
DOI: 10.2147/DMSO.S438818 -
Blood Cancer Journal May 2024Acute myeloid leukemia (AML) with t(9;22) (q34.1; q11.2)/BCR::ABL1, a distinct entity within the group of AML with defining genetic abnormalities, belong to the...
Acute myeloid leukemia (AML) with t(9;22) (q34.1; q11.2)/BCR::ABL1, a distinct entity within the group of AML with defining genetic abnormalities, belong to the adverse-risk group of the 2022 ELN classification. However, there is little data on outcome since the era of tyrosine kinase inhibitors. Among 5819 AML cases included in the DATAML registry, 20 patients with de novo BCR::ABL1AML (0.3%) were identified. Eighteen patients treated with standard induction chemotherapy were analyzed in this study. Imatinib was added to chemotherapy in 16 patients. The female-to-male ratio was 1.25 and median age was 54 years. The t(9;22) translocation was the sole chromosomal abnormality in 12 patients. Main gene mutations detected by NGS were ASXL1, RUNX1 and NPM1. Compared with patients with myeloid blast phase of chronic myeloid leukemia (CML-BP), de novo BCR::ABL1AML had higher WBC, fewer additional chromosomal abnormalities, lower CD36 or CD7 expression and no ABL1 mutations. Seventeen patients (94.4%) achieved complete remission (CR) or CR with incomplete hematologic recovery. Twelve patients were allografted in first remission. With a median follow-up of 6.3 years, the median OS was not reached and 2-year OS was 77% (95% CI: 50-91). Four out of five patients who were not transplanted did not relapse. Comparison of BCR::ABL1AML, CML-BP, 2017 ELN intermediate (n = 643) and adverse-risk patients (n = 863) showed that patients with BCR::ABL1AML had a significant better outcome than intermediate and adverse-risk patients. BCR::ABL1AML patients treated with imatinib and intensive chemotherapy should not be included in the adverse-risk group of current AML classifications.
Topics: Humans; Male; Female; Middle Aged; Adult; Imatinib Mesylate; Aged; Leukemia, Myeloid, Acute; Translocation, Genetic; Registries; Chromosomes, Human, Pair 22; Fusion Proteins, bcr-abl; Antineoplastic Combined Chemotherapy Protocols; Chromosomes, Human, Pair 9; Young Adult; Nucleophosmin
PubMed: 38821940
DOI: 10.1038/s41408-024-01069-9