1,215 results match your criteria transcriptional abnormality

Lactoferrin is required for early B cell development in C57BL/6 mice.

J Hematol Oncol 2021 Apr 7;14(1):58. Epub 2021 Apr 7.

Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

Lactoferrin (Lf) is widely distributed in mammalian milk, various tissues, and their exocrine fluids and has many physiological functions, such as bacteriostasis, antivirus, and immunoregulation. Here, we provide evidence that lactoferrin is required for early stages of B cell development in mice. Lactoferrin-deficient (Lf) C57BL/6 mice showed systematic reduction in total B cells, which was attributed to the arrest of early B cell development from pre-pro-B to pro-B stage. Read More

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Mitochondrial Dysfunction in Huntington's disease: Pathogenesis and Therapeutic Opportunities.

Curr Drug Targets 2021 Feb 23. Epub 2021 Feb 23.

Department of Pharmacy, Faculty of Pharmacy, University of Oradea. Romania.

Huntington's disease (HD) is prototypical neurodegenerative disease, preferentially disrupts the neurons of striatum and cor-tex. Progressive motor dysfunctions, psychiatric disturbances, behavioural impairments and cognitive decline are the clinical symptoms of HD progression. The disease occurs due to, expanded CAG repeats in exon 1 of huntingtin protein (mHtt) causing its aggregation. Read More

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February 2021

Metabolomics reveals the reproductive abnormality in female zebrafish exposed to environmentally relevant levels of climbazole.

Environ Pollut 2021 Apr 5;275:116665. Epub 2021 Feb 5.

Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, School of Environmental Science and Engineering, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou, 510006, China; State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong Special Administrative Region, China.

Climbazole (CBZ) ubiquitously detected in the aquatic environment may disrupt fish reproductive function. Thus far, the previous study has focused on its transcriptional impact of steroidogenesis-related genes on zebrafish, but the underlying toxic mechanism still needs further investigation at the metabolic level. In this study, adult zebrafish were chronically exposed to CBZ at concentrations of 0. Read More

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A novel variant of causes a severe neurodevelopmental disorder with infantile spasms.

Cold Spring Harb Mol Case Stud 2021 Apr 8;7(2). Epub 2021 Apr 8.

Cipher Gene Ltd., Beijing, China.

Infantile spasms are a potentially catastrophic form of epilepsy syndrome that are usually associated with substantial developmental delay and commonly occur in children younger than 1 yr. Recent reports on four cases revealed that variants harbored in a novel gene were causative for the syndrome. We report a fifth affected individual, a 10-mo-old male patient who presented with a neurodevelopmental syndrome characterized by infantile spasms. Read More

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[Clinical characterization and genetic analysis of a newborn with chromosome 8q21.11 deletion syndrome].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Feb;38(2):145-149

Medical Genetics Center, Shenzhen Maternal and Child Health Care Hospital Affiliated to Southern Medical University, Shenzhen, Guangdong 518017, China.

Objective: To explore the genetic etiology for a newborn with corneal opacity.

Methods: The neonate and her parents were subjected to routine G-banding chromosomal karyotyping analysis. Copy number variation (CNV) was analyzed with low-coverage whole-genome sequencing (WGS) and single nucleotide polymorphism microarray (SNP array). Read More

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February 2021

Toll-like receptor 4 signaling activates ERG function in prostate cancer and provides a therapeutic target.

NAR Cancer 2021 Mar 27;3(1):zcaa046. Epub 2021 Jan 27.

Medical Sciences, Indiana University School of Medicine, Bloomington, IN 47405, USA.

The gene fusion and subsequent overexpression of the ERG transcription factor occurs in ∼50% of prostate tumors, making it the most common abnormality of the prostate cancer genome. While ERG has been shown to drive tumor progression and cancer-related phenotypes, as a transcription factor it is difficult to target therapeutically. Using a genetic screen, we identified the toll-like receptor 4 (TLR4) signaling pathway as important for ERG function in prostate cells. Read More

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Synergistic inhibition of histone modifiers produces therapeutic effects in adult Shank3-deficient mice.

Transl Psychiatry 2021 Feb 4;11(1):99. Epub 2021 Feb 4.

Department of Physiology and Biophysics, State University of New York at Buffalo, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, 14203, USA.

Autism spectrum disorder (ASD) is a lifelong developmental disorder characterized by social deficits and other behavioral abnormalities. Dysregulation of epigenetic processes, such as histone modifications and chromatin remodeling, have been implicated in ASD pathology, and provides a promising therapeutic target for ASD. Haploinsufficiency of the SHANK3 gene is causally linked to ASD, so adult (3-5 months old) Shank3-deficient male mice were used in this drug discovery study. Read More

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February 2021

Genetic and Epigenetic Characteristics of Autosomal Dominant Pseudohypoparathyroidism Type 1B: Case Reports and Literature Review.

Horm Metab Res 2021 Apr 29;53(4):225-235. Epub 2021 Jan 29.

Department of Endocrinology and Metabolism, Shandong University, Jinan, Shandong, China.

Autosomal dominant pseudohypoparathyroidism 1B (AD-PHP1B) is a rare endocrine and imprinted disorder. The objective of this study is to clarify the imprinted regulation of the guanine nucleotide binding-protein α-stimulating activity polypeptide 1 (GNAS) cluster in the occurrence and development of AD-PHP1B based on animal and clinical patient studies. The methylation-specific multiples ligation-dependent probe amplification (MS-MLPA) was conducted to detect the copy number variation in syntaxin-16 (STX16) gene and methylation status of the GNAS differentially methylated regions (DMRs). Read More

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Emerging physiological and pathological roles of MeCP2 in non-neurological systems.

Arch Biochem Biophys 2021 03 21;700:108768. Epub 2021 Jan 21.

Tongji School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Tongji-Rongcheng Biomedicine Research Center, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address:

Numerous neurological and non-neurological disorders are associated with dysfunction of epigenetic modulators, and methyl CpG binding protein 2 (MeCP2) is one of such proteins. Initially identified as a transcriptional repressor, MeCP2 specifically binds to methylated DNA, and mutations of MeCP2 have been shown to cause Rett syndrome (RTT), a severe neurological disorder. Recently, accumulating evidence suggests that ubiquitously expressed MeCP2 also plays a central role in non-neurological disorders including cardiac dysfunction, liver injury, respiratory disorders, urological dysfunction, adipose tissue metabolism disorders, movement abnormality and inflammatory responses in a DNA methylation dependent or independent manner. Read More

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Cholesterol Review: A Metabolically Important Molecule.

Endocr Pract 2020 Dec;26(12):1514-1523

From the (1)University of New Mexico School of Medicine, Department of Internal Medicine, Division of Endocrinology and Metabolism, Albuquerque, New Mexico, and the.

Objective: Cholesterol is an important molecule in humans and both its excess and its deficiency cause disease. Most clinicians appreciate its role in stabilizing cellular plasma membranes but are unaware of its myriad other functions.

Methods: This review highlights cholesterol's newly recognized important roles in human physiology and pathophysiology. Read More

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December 2020

Pcresol and Indoxyl Sulfate Impair Osteogenic Differentiation by Triggering Mesenchymal Stem Cell Senescence.

Int J Med Sci 2021 1;18(3):744-755. Epub 2021 Jan 1.

Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Salaya, Nakhon Pathom, Thailand.

Chronic kidney disease (CKD) patients obtained high levels of uremic toxins progressively develop several complications including bone fractures. Protein-bound uremic toxins especially p-cresol and indoxyl sulfate are hardly eliminated due to their high molecular weight. Thus, the abnormality of bone in CKD patient could be potentially resulted from the accumulation of uremic toxins. Read More

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January 2021

Severe early onset obesity and hypopituitarism in a child with a novel SIM1 gene mutation.

Endocrinol Diabetes Metab Case Rep 2020 Oct 6;2020. Epub 2020 Oct 6.

Division of Endocrinology, Phoenix Children's Hospital, Phoenix, Arizona, USA.

Summary: Single-minded homolog 1 (SIM1) is a transcription factor that plays a role in the development of both the hypothalamus and pituitary. SIM1 gene mutations are known to cause obesity in humans, and chromosomal deletions encompassing SIM1 and other genes necessary for pituitary development can cause a Prader-Willi-like syndrome with obesity and hypopituitarism. There have been no reported cases of hypopituitarism linked to a single SIM1 mutation. Read More

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October 2020

Abnormal Neutrophil Transcriptional Signature May Predict Newly Diagnosed Latent Autoimmune Diabetes in Adults of South China.

Front Endocrinol (Lausanne) 2020 18;11:581902. Epub 2020 Dec 18.

National Clinical Research Center for Metabolic Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.

Objective: Latent autoimmune diabetes in adults (LADA) is an autoimmune diabetes characterized by slowly progressive of β-cell function deterioration. Our previous finding demonstrated that neutrophil numbers and migration abilities display distinct levels in different types of diabetes, including LADA, whereas its pathological alterations in the development of LADA remain unknown. We aimed to investigate the changes in transcriptional levels of peripheral neutrophils in newly diagnosed LADA. Read More

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December 2020

Quantitative polymerase Chain reaction profiling of microRNAs in peripheral lymph-monocytes from MGUS subjects.

Pathol Res Pract 2021 Feb 13;218:153317. Epub 2020 Dec 13.

Division of Hematology, Department of Human Pathology in Adulthood and Childhood, University of Messina, Località Gazzi, Via Consolare Valeria, Messina, Italy.

Monoclonal gammopathy of undetermined significance (MGUS) is a pre-malignant abnormality of plasma cells, with increased serum levels of immunoglobulins. Patients with MGUS may evolve to multiple myeloma through a multistep process including deregulated gene expression. microRNAs are small non-coding RNA molecules involved in post-transcriptional regulation of crucial biological processes, such as morphogenesis, cell differentiation, apoptosis, and cancer. Read More

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February 2021

GenHITS: A network science approach to driver gene detection in human regulatory network using gene's influence evaluation.

J Biomed Inform 2021 Feb 14;114:103661. Epub 2020 Dec 14.

Department of Information Technology Engineering, School of Systems and Industrial Engineering, Tarbiat Modares University (TMU), Tehran, Iran.

Cancer is among the diseases causing death, in which, cells uncontrollably grow and reproduce beyond the cell regulatory mechanism. In this disease, some genes are initiators of abnormalities and then transmit them to other genes through protein interactions. Accordingly, these genes are known as cancer driver genes (CDGs). Read More

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February 2021

Novel GATA6-FOXO1 fusions in a subset of epithelioid hemangioma.

Mod Pathol 2021 May 14;34(5):934-941. Epub 2020 Dec 14.

Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.

The genetic hallmark of epithelioid hemangioma (EH) is the presence of recurrent gene fusions involving FOS and FOSB transcription factors, which occur in one-third of the cases. Certain clinical, pathologic, and genotypic correlations have been described, with FOS-related fusions being more often detected in skeletal and cellular variants of EH, while FOSB gene rearrangements are more commonly associated with atypical histologic features and penile location. These fusions are infrequently detected in the cutaneous or head and neck EH. Read More

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Case Report: Characterization of a Novel NONO Intronic Mutation in a Fetus With X-Linked Syndromic Mental Retardation-34.

Front Genet 2020 16;11:593688. Epub 2020 Nov 16.

Beijing Anzhen Hospital, Capital Medical University, Beijing, China.

Background: The NONO gene is located on chromosome Xq13.1 and encodes a nuclear protein involved in RNA synthesis, transcriptional regulation, and DNA repair. Hemizygous variants in NONO have been reported to cause mental retardation, X-linked, syndromic 34 (MRXS34) in males. Read More

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November 2020

Chromosomal aberration arises during somatic reprogramming to pluripotent stem cells.

Cell Div 2020 Nov 3;15(1):12. Epub 2020 Nov 3.

Key Laboratory of Organ Development and Regeneration of Zhejiang Province, College of Life and Environmental Sciences, Hangzhou Normal University, 311121, Hangzhou, China.

Background: Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) has opened new therapeutic possibilities. However, karyotypic abnormalities detected in iPSCs compromised their utility, especially chromosomal aberrations found at early passages raised serious safety concerns. The mechanism underlying the chromosomal abnormality in early-passage iPSCs is not known. Read More

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November 2020

Genetic and Pathological Characteristic Patterns of a Family With Neuronal Intranuclear Inclusion Disease.

J Neuropathol Exp Neurol 2020 12;79(12):1293-1302

From the Department of Neurology, Affiliated Nanjing Brain Hospital, Nanjing Medical University.

Neuronal intranuclear inclusion disease (NIID) is a rare, progressive neurodegenerative disorder. This study aimed to investigate clinical, imaging, genetic, and dermatopathological characteristics of a family with adult-onset NIID. The proband was a 62-year-old woman with 3 brothers and 2 sisters. Read More

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December 2020

Elucidation of a Novel Role of YebC in Surface Polysaccharides Regulation of -Deletion.

Front Microbiol 2020 9;11:597515. Epub 2020 Nov 9.

Microbiological Resource Research Institute, Pusan National University, Busan, South Korea.

The BipA (BPI-inducible protein A) protein is ubiquitously conserved in various bacterial species and belongs to the translational GTPase family. Interestingly, the function of BipA is not essential for cell growth under normal growth conditions. However, cultivation of -deleted cells at 20°C leads to cold-sensitive growth defect and several phenotypic changes in ribosome assembly, capsule production, and motility, suggesting its global regulatory roles. Read More

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November 2020

Triclosan leads to dysregulation of the metabolic regulator FGF21 exacerbating high fat diet-induced nonalcoholic fatty liver disease.

Proc Natl Acad Sci U S A 2020 12 23;117(49):31259-31266. Epub 2020 Nov 23.

Laboratory of Environmental Toxicology, Department of Pharmacology, University of California San Diego, La Jolla, CA 92093;

Triclosan (TCS), employed as an antiseptic and disinfectant, comes into direct contact with humans through a plethora of consumer products and its rising environmental release. We have demonstrated that TCS promotes liver tumorigenesis in mice, yet the biological and molecular mechanisms by which TCS exerts its toxicity, especially in early stages of liver disease, are largely unexplored. When mice were fed a high-fat diet (HFD), we found that fatty liver and dyslipidemia are prominent early signs of liver abnormality induced by TCS. Read More

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December 2020

The effect of Rbfox2 modulation on retinal transcriptome and visual function.

Sci Rep 2020 11 12;10(1):19683. Epub 2020 Nov 12.

Stein Eye Institute, University of California, Los Angeles, 100 Stein Plaza, Los Angeles, CA, 90095, USA.

Rbfox proteins regulate alternative splicing, mRNA stability and translation. These proteins are involved in neurogenesis and have been associated with various neurological conditions. Here, we analyzed Rbfox2 expression in adult and developing mouse retinas and the effect of its downregulation on visual function and retinal transcriptome. Read More

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November 2020

Whole transcriptome sequencing detects a large number of novel fusion transcripts in patients with AML and MDS.

Blood Adv 2020 11;4(21):5393-5401

MLL Munich Leukemia Laboratory, Munich, Germany; and.

Fusion transcripts are frequent genetic abnormalities in myeloid malignancies and are often the basis for risk stratification, minimal residual disease (MRD) monitoring, and targeted therapy. We comprehensively analyzed the fusion transcript landscape in 572 acute myeloid leukemia (AML) and 630 myelodysplastic syndrome (MDS) patients by whole transcriptome sequencing (WTS). Totally, 274 fusion events (131 unique fusions) were identified in 210/572 AML patients (37%). Read More

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November 2020

Radiogenomics of lung cancer.

J Thorac Dis 2020 Sep;12(9):5104-5109

Department of Applied AI and Data Science, City of Hope National Medical Center, Duarte, CA, USA.

Machine learning (ML) and artificial intelligence (AI) are aiding in improving sensitivity and specificity of diagnostic imaging. The rapid adoption of these advanced ML algorithms is transforming imaging analysis; taking us from noninvasive detection of pathology to noninvasive precise diagnosis of the pathology by identifying whether detected abnormality is a secondary to infection, inflammation and/or neoplasm. This is led to the emergence of "Radiobiogenomics"; referring to the concept of identifying biologic (genomic, proteomic) alterations in the detected lesion. Read More

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September 2020

EWSR1 overexpression is a pro-oncogenic event in multiple myeloma.

Int J Hematol 2021 Mar 23;113(3):381-394. Epub 2020 Oct 23.

Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.

Multiple myeloma (MM) is cytogenetically, genetically and molecularly heterogenous even among subclones in one patient, therefore, it is essential to identify both frequent and patient-specific drivers of molecular abnormality. Following previous molecular investigations, we in this study investigated the expression patterns and function of the Ewing sarcoma breakpoint region 1 (EWSR1) gene in MM. The EWSR1 transcriptional level in CD138-positive myeloma cells was higher in 36. Read More

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Expanding the phenotype of Wiedemann-Steiner syndrome: Craniovertebral junction anomalies.

Am J Med Genet A 2020 12 11;182(12):2877-2886. Epub 2020 Oct 11.

Medical Genetics Unit, Meyer Children's University Hospital, Florence, Italy.

Wiedemann-Steiner syndrome (WDSTS) is a rare autosomal dominant condition caused by heterozygous loss of function variants in the KMT2A (MLL) gene, encoding a lysine N-methyltransferase that mediates a histone methylation pattern specific for epigenetic transcriptional activation. WDSTS is characterized by a distinctive facial phenotype, hypertrichosis, short stature, developmental delay, intellectual disability, congenital malformations, and skeletal anomalies. Recently, a few patients have been reported having abnormal skeletal development of the cervical spine. Read More

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December 2020

Molecular Profiling of Clear Cell Myoepithelial Carcinoma of Salivary Glands With EWSR1 Rearrangement Identifies Frequent PLAG1 Gene Fusions But No EWSR1 Fusion Transcripts.

Am J Surg Pathol 2021 01;45(1):1-13

Institute of Biomedicine, University of Turku.

Myoepithelial carcinoma of salivary glands is an underrecognized and challenging entity with a broad morphologic spectrum, including an EWSR1-rearranged clear cell variant. Myoepithelial carcinoma is generally aggressive with largely unknown genetic features. A retrospective review of Salivary Gland Tumor Registry in Pilsen searching for the key words "clear cell myoepithelial carcinoma," "hyalinizing clear cell," and "clear cell malignant myoepithelioma" yielded 94 clear cell myoepithelial carcinomas (CCMCs) for molecular analysis of EWSR1 rearrangement using fluorescence in situ hybridization (FISH). Read More

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January 2021

Silencing of Testin expression is a frequent event in spontaneous lymphomas from Trp53-mutant mice.

Sci Rep 2020 10 1;10(1):16255. Epub 2020 Oct 1.

Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.

The tumour suppressor gene, TES, is frequently methylated in many human tumours. Previously, we demonstrated that TES promoter methylation and transcriptional silencing was the most common molecular abnormality detected in childhood acute lymphoblastic leukaemia (ALL). Trp53-mutant mouse models predominantly develop B- and T-cell lymphomas, which are widely considered equivalent to childhood T and B ALL. Read More

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October 2020

Recurrent YAP1 and MAML2 Gene Rearrangements in Retiform and Composite Hemangioendothelioma.

Am J Surg Pathol 2020 12;44(12):1677-1684

Department of Pathology, Brigham and Women's Hospital, Boston, MA.

Retiform and composite hemangioendotheliomas (CHEs) are both locally aggressive, rarely metastasizing vascular neoplasms characterized by arborizing vascular channels lined by endothelial cells with a hobnail morphology. CHE displays additional cytologic and architectural components, including often vacuolated epithelioid cells, solid areas, or features reminiscent of well-differentiated angiosarcoma. Triggered by an index case of a soft tissue retiform hemangioendothelioma (RHE) which revealed a YAP1-MAML2 gene fusion by targeted RNA sequencing, we sought to investigate additional cases in this morphologic spectrum for this genetic abnormality. Read More

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December 2020