538 results match your criteria referred mutated

A competitive hemagglutination inhibition assay for dissecting functional antibody activity to influenza virus.

J Virol 2021 Sep 15:JVI0237920. Epub 2021 Sep 15.

Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USA.

Influenza remains one of the most contagious infectious diseases. Approximately, 25-50 million people suffer from influenza-like illness in the United States annually, leading to almost 1 million hospitalizations. Globally, the World Health Organization (WHO) estimates 250,000-500,000 mortalities associated with secondary respiratory complications due to influenza virus infection every year. Read More

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September 2021

Lipid Metabolism Regulates Oxidative Stress and Ferroptosis in RAS-Driven Cancers: A Perspective on Cancer Progression and Therapy.

Front Mol Biosci 2021 16;8:706650. Epub 2021 Aug 16.

Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States.

, and , collectively referred to as oncogenic RAS, are the most frequently mutated driver proto-oncogenes in cancer. Oncogenic RAS aberrantly rewires metabolic pathways promoting the generation of intracellular reactive oxygen species (ROS). In particular, lipids have gained increasing attention serving critical biological roles as building blocks for cellular membranes, moieties for post-translational protein modifications, signaling molecules and substrates for ß-oxidation. Read More

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BRCAness as a Biomarker of Susceptibility to PARP Inhibitors in Glioblastoma Multiforme.

Biomolecules 2021 08 11;11(8). Epub 2021 Aug 11.

Department of Oncology, Radiobiology Research Institute, University of Oxford, Oxford OX3 7LJ, UK.

Glioblastoma multiforme (GBM) is the most common primary brain cancer. GBMs commonly acquire resistance to standard-of-care therapies. Among the novel means to sensitize GBM to DNA-damaging therapies, a promising strategy is to combine them with inhibitors of the DNA damage repair (DDR) machinery, such as inhibitors for poly(ADP-ribose) polymerase (PARP). Read More

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Association of EGFR Tyrosine Kinase Inhibitor Treatment With Progression-Free Survival Among Taiwanese Patients With Advanced Lung Adenocarcinoma and EGFR Mutation.

Front Pharmacol 2021 9;12:720687. Epub 2021 Aug 9.

Master Program in Clinical Pharmacy, School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.

There is limited data on the relative survival rate of first-line therapy of gefitinib, erlotinib (first-generation epidermal growth factor receptor-tyrosine kinase inhibitor [EGFR-TKI]), and afatinib (second-generation EGFR-TKI) in patients with EGFR-mutated advanced lung adenocarcinoma in real-world data, especially in the Asian population. This study aimed to compare the relative survival rate of gefitinib, erlotinib, and afatinib in patients with EGFR-mutated advanced lung adenocarcinoma by real-world data in Taiwan. This retrospective cohort population-based study included untreated adult patients diagnosed with advanced lung adenocarcinoma who were identified in the Taiwan National Health Insurance Research Database between 2014 and 2017. Read More

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Clinical, cytogenetic and molecular findings in nine Moroccan patients with Fanconi anemia.

Pan Afr Med J 2021 26;39:72. Epub 2021 May 26.

Centre de Recherche en Génomique et Pathologies Humaines (Centre GENOPATH), Faculté de Médecine et de Pharmacie, Université Mohammed V, Rabat, Maroc.

Introduction: Fanconi anemia (FA) is a rare inherited hematological disease due to a defect in the DNA repair pathway resulting in congenital abnormalities and high susceptibility to develop cancers. The cytogenetic analysis using alkylating agents is still a reference test to establish the diagnosis. Despite the genetic heterogeneity, the identification of the causal mutation is actually performed especially after the development of next generation sequencing (NGS). Read More

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September 2021

Fragile X Syndrome in a Female With Homozygous Full-Mutation Alleles of the FMR1 Gene.

Cureus 2021 Jul 12;13(7):e16340. Epub 2021 Jul 12.

Medical Genetics Laboratory, Genetic Foundation of Khorasan Razavi, Mashhad, IRN.

Fragile X syndrome (FXS) has been reported as the leading cause of mental retardation (MR) that predominantly involves males compared to females. An over-expansion of CGG repeats in the 5' untranslated region of the FMR1 gene plays the primary role in this disease. In this study, we encountered a homozygote female patient affected by FMR1 expansion mutation. Read More

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Radical Resection for Second EGFR-mutated Primary Lung Cancer Following Immune Checkpoint Inhibitor Monotherapy for Stage IV Lung Adenocarcinoma.

Intern Med 2021 Aug 13. Epub 2021 Aug 13.

Department of Respiratory Medicine, NTT-East Corporation Sapporo Medical Center, Japan.

A 78-year-old woman with multiple lung nodules, epithelial growth factor receptor (EGFR) exon 20 insertion mutations, and diagnosed with advanced lung adenocarcinoma (cT4N3M1a, stage IVA), was referred to our hospital. She received immune checkpoint inhibitor (ICI) therapy. The therapy showed remarkable antitumor effects; only a single nodule remained in the right upper lobe. Read More

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The Clinical Application of Neoantigens in Esophageal Cancer.

Front Oncol 2021 27;11:703517. Epub 2021 Jul 27.

Department of Thoracic Surgery, West China Hospital of Sichuan University, Chengdu, China.

Esophageal cancer (EC) is a common malignant tumor with poor prognosis, and current treatments for patients with advanced EC remain unsatisfactory. Recently, immunotherapy has been recognized as a new and promising approach for various tumors. EC cells present a high tumor mutation burden and harbor abundant tumor antigens, including tumor-associated antigens and tumor-specific antigens. Read More

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Heterozygous HTRA1 nonsense or frameshift mutations are pathogenic.

Brain 2021 Jul 16. Epub 2021 Jul 16.

AP-HP, Service de Génétique Moléculaire Neurovasculaire, Hôpital Saint-Louis, France.

Heterozygous missense HTRA1 mutations have been associated with an autosomal dominant cerebral small vessel disease whereas the pathogenicity of heterozygous HTRA1 stop codon variants is unclear. We performed a targeted high throughput sequencing of all known cerebral small vessel disease genes, including HTRA1, in 3,853 unrelated consecutive CSVD patients referred for molecular diagnosis. The frequency of heterozygous HTRA1 mutations leading to a premature stop codon in this patient cohort was compared with their frequency in large control databases. Read More

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Leukemic Variant of Mantle Cell Lymphoma: Clinical Presentation and Management.

Curr Oncol Rep 2021 Jul 16;23(9):102. Epub 2021 Jul 16.

Division of Hematology/Oncology, Department of Medicine, University of Virginia Cancer Center, Jefferson Park Avenue, PO 800716, Charlottesville, VA, 22908, USA.

Purpose Of Review: This review summarizes the unique presentation and management of the leukemic variant of mantle cell lymphoma (LV-MCL, also referred to as non-nodal MCL) and highlights the biologic and clinical differentiation from classical mantle cell lymphoma (cMCL) in biomarker expression, clinical features, prognosis, disease course, and treatment.

Recent Findings: Several studies have evaluated the gene expression profile of mantle cell lymphoma, differentiating LV-MCL from cMCL. The typical immunophenotypic profile is CD5-positive, SOX 11-negative, CD23-low, CD200-low, and cyclin D1 overexpressed. Read More

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Diagnostic Challenge and Clinical Dilemma: The Long Reach of Clonal Hematopoiesis.

Clin Chem 2021 Aug;67(8):1062-1070

Department of Pathology, University of Utah and ARUP Laboratories, Salt Lake City, UT.

Background: Widespread application of massively parallel sequencing has resulted in recognition of clonal hematopoiesis in various clinical settings and on a relatively frequent basis. Somatic mutations occur in individuals with normal blood counts, and increase in frequency with age. The genes affected are the same genes that are commonly mutated in overt myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Read More

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Complex Modes of Inheritance in Hereditary Red Blood Cell Disorders: A Case Series Study of 155 Patients.

Genes (Basel) 2021 Jun 23;12(7). Epub 2021 Jun 23.

Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, 80131 Napoli, Italy.

Hereditary erythrocytes disorders include a large group of conditions with heterogeneous molecular bases and phenotypes. We analyzed here a case series of 155 consecutive patients with clinical suspicion of hereditary erythrocyte defects referred to the Medical Genetics Unit from 2018 to 2020. All of the cases followed a diagnostic workflow based on a targeted next-generation sequencing panel of 86 genes causative of hereditary red blood cell defects. Read More

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Engineered pH-Sensitive Protein G/IgG Interaction.

ACS Chem Biol 2021 07 21;16(7):1142-1146. Epub 2021 Jun 21.

Bioscience Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, United States.

While natural protein-protein interactions have evolved to be induced by complex stimuli, rational design of interactions that can be switched-on-demand still remain challenging in the protein design world. Here, we demonstrate that a computationally redesigned natural interface for improved binding affinity could further be mutated to adopt a pH switchable interaction. The redesigned interface of Protein G/human IgG Fc domain (referred to as PrG/hIgG), when incorporated with histidine and glutamic acid on PrG (PrG-EHHE), showed a switch in binding affinity by 50-fold when the pH was altered from mild acidic to mild basic. Read More

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The implications of IDH mutations for cancer development and therapy.

Nat Rev Clin Oncol 2021 Oct 15;18(10):645-661. Epub 2021 Jun 15.

Department of Pathology, Duke University Medical Center, Durham, NC, USA.

Mutations in the genes encoding the cytoplasmic and mitochondrial forms of isocitrate dehydrogenase (IDH1 and IDH2, respectively; collectively referred to as IDH) are frequently detected in cancers of various origins, including but not limited to acute myeloid leukaemia (20%), cholangiocarcinoma (20%), chondrosarcoma (80%) and glioma (80%). In all cases, neomorphic activity of the mutated enzyme leads to production of the oncometabolite D-2-hydroxyglutarate, which has profound cell-autonomous and non-cell-autonomous effects. The broad effects of IDH mutations on epigenetic, differentiation and metabolic programmes, together with their high prevalence across a variety of cancer types, early presence in tumorigenesis and uniform expression in tumour cells, make mutant IDH an ideal therapeutic target. Read More

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October 2021

Potent germline-like monoclonal antibodies: rapid identification of promising candidates for antibody-based antiviral therapy.

Antib Ther 2021 Apr 17;4(2):89-98. Epub 2021 May 17.

MOE/NHC Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.

In recent years, fully human monoclonal antibodies (mAbs) are making up an increasing share of the pharmaceutical market. However, to improve affinity and efficacy of antibodies, many somatic hypermutations could be introduced during affinity maturation, which cause several issues including safety and efficacy and limit their application in clinic. Here, we propose a special class of human mAbs with limited level of somatic mutations, referred to as germline-like mAbs. Read More

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Current Applications and Future Perspectives of CRISPR-Cas9 for the Treatment of Lung Cancer.

Biologics 2021 31;15:199-204. Epub 2021 May 31.

Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia.

Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated proteins are referred to as CRISPR-Cas9. Bacteria and archaea have an adaptive (acquired) immune system. As a result, developing the best single regulated RNA and Cas9 endonuclease proteins and implementing the method in clinical practice would aid in the treatment of diseases of various origins, including lung cancers. Read More

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TaqMan real time PCR for the Detection of the Gilbert's Syndrome Markers UGT1A1*28; UGT1A1*36 and UGT1A1*37.

Mol Biol Rep 2021 May 4;48(5):4953-4959. Epub 2021 Jun 4.

Department of Public Health and Pediatrics, School of Medicine, University of Turin, Piazza Polonia 94, 10126, Turin, Italy.

Gilbert's syndrome is characterized by mild unconjugated hyperbilirubinemia. The key of this disease is a diminished activity of UDP-glucuronosyltransferase 1A1 (UGT1A1). TA insertion into the TATA box promoter region of the UGT1A1 gene on chromosome 2 is the genetic basis of Gilbert's syndrome (UGT1A1*28). Read More

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Clinical and genetic spectrum of a Chinese cohort with SCN4A gene mutations.

Neuromuscul Disord 2021 Apr 15. Epub 2021 Apr 15.

Department of Clinical Electrophysiology, Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, 200040, China. Electronic address:

Skeletal muscle sodium channelopathies due to SCN4A gene mutations have a broad clinical spectrum. However, each phenotype has been reported in few cases of Chinese origin. We present detailed phenotype and genotype data from a cohort of 40 cases with SCN4A gene mutations seen in neuromuscular diagnostic service in Huashan hospital, Fudan University. Read More

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Prediction of Target-Drug Therapy by Identifying Gene Mutations in Lung Cancer With Histopathological Stained Image and Deep Learning Techniques.

Front Oncol 2021 13;11:642945. Epub 2021 Apr 13.

Key Laboratory of Computational Science and Application of Hainan Province, Haikou, China.

Lung cancer is a kind of cancer with high morbidity and mortality which is associated with various gene mutations. Individualized targeted-drug therapy has become the optimized treatment of lung cancer, especially benefit for patients who are not qualified for lung lobectomy. It is crucial to accurately identify mutant genes within tumor region from stained pathological slice. Read More

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The power of three-dimensional printing technology in functional restoration of rare maxillomandibular deformity due to genetic disorder: a case report.

J Med Case Rep 2021 Apr 12;15(1):197. Epub 2021 Apr 12.

Oral and Maxillofacial Surgery, Oral Medicine Institute, Galilee Medical Center, Nahariya, Israel.

Background: Thalassemia is an inherited autosomal recessive blood disorder causing abnormal formation of hemoglobin, known as a syndrome of anemia with microcytic erythrocytes. It is the most common genetic disorder worldwide, with a high prevalence among individuals of Mediterranean descent. The state of homozygosity of the beta-globin mutated gene is known as beta-thalassemia major, and these patients require regular blood transfusions and iron chelation therapy for survival. Read More

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A Case of Dominant Dystrophic Epidermolysis Bullosa with a G2043R Mutation in the Type VII Collagen Gene.

Acta Dermatovenerol Croat 2020 Dec;28(4):251-252

Sayaka Yamaguchi, MD, PhD, Department of Dermatology Graduate School and Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0125, Japan;

Dear Editor, Dystrophic epidermolysis bullosa (DEB) is a subepidermal bulla, characterized by severe itching, lichenoid or nodular prurigo-like lesions, skin erosion, scars, milia, and nail dystrophy, resulting from COL7A1 mutation. Herein, we report a case of dominant DEB with a G2043R mutation in COL7A1. A-25-year-old Japanese woman was referred to our clinic for recurrent intense pruritis and hypertrophic scars on the abdomen (Figure 1, a). Read More

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December 2020

Triple-Negative Essential Thrombocythemia: Clinical-Pathological and Molecular Features. A Single-Center Cohort Study.

Front Oncol 2021 12;11:637116. Epub 2021 Mar 12.

Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Lack of demonstrable mutations affecting , or driver genes within the spectrum of -negative myeloproliferative neoplasms (MPNs) is currently referred to as a triple-negative genotype, which is found in about 10% of patients with essential thrombocythemia (ET) and 5-10% of those with primary myelofibrosis (PMF). Very few papers are presently available on triple-negative ET, which is basically described as an indolent disease, differently from triple-negative PMF, which is an aggressive myeloid neoplasm, with a significantly higher risk of leukemic evolution. The aim of the present study was to evaluate the bone marrow morphology and the clinical-laboratory parameters of triple-negative ET patients, as well as to determine their molecular profile using next-generation sequencing (NGS) to identify any potential clonal biomarkers. Read More

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Real-World Performance Assessment of Xpert MTB/RIF Assay for Detecting Pulmonary Tuberculosis and Rifampin Resistance in a Single Tertiary Care Hospital in Korea.

Jpn J Infect Dis 2021 Mar 31. Epub 2021 Mar 31.

Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Korea.

This study aimed at evaluating performance of Xpert MTB/RIF (Xpert) regarding detection of pulmonary tuberculosis compared to acid-fast bacilli (AFB) smear and culture, and concordance of rifampin resistance with drug susceptibility test. Specimens simultaneously referred for AFB smear, culture, and Xpert during April 2015 to March 2018 were retrospectively reviewed. Sensitivity, specificity, and mean cycle-threshold (C) values of Xpert and rifampin resistance results were analyzed. Read More

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Flow cytometric immunophenotypic alterations of persistent clonal haematopoiesis in remission bone marrows of patients with NPM1-mutated acute myeloid leukaemia.

Br J Haematol 2021 03 22;192(6):1054-1063. Epub 2021 Feb 22.

The Department of Hematopathology, MD Anderson Cancer Center, Houston, TX, USA.

Clonal haematopoiesis (CH) in patients with acute myeloid leukaemia (AML) may persist beyond attaining complete remission. From a consecutive cohort of 67 patients with nucleophosmin 1-mutated (NPM1 ) AML, we identified 50 who achieved NPM1 clearance and had parallel multicolour flow cytometry (MFC) and next generation sequencing (NGS). In total, 13 (26%) cleared all mutations, 37 (74%) had persistent CH frequently involving DNA methyltransferase 3α (DNMT3A,70%), tet methylcytosine dioxygenase 2 (TET2, 27%), isocitrate dehydrogenase 2 (IDH2, 19%) and IDH1 (11%). Read More

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Dual proteotoxic stress accelerates liver injury via activation of p62-Nrf2.

J Pathol 2021 May 18;254(1):80-91. Epub 2021 Mar 18.

Department of Medicine III, University Hospital Aachen, Aachen, Germany.

Protein accumulation is the hallmark of various neuronal, muscular, and other human disorders. It is also often seen in the liver as a major protein-secretory organ. For example, aggregation of mutated alpha1-antitrypsin (AAT), referred to as PiZ, is a characteristic feature of AAT deficiency, whereas retention of hepatitis B surface protein (HBs) is found in chronic hepatitis B (CHB) infection. Read More

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Immunophenotypic Spectrum and Genomic Landscape of Refractory Celiac Disease Type II.

Am J Surg Pathol 2021 07;45(7):905-916

Department of Pathology and Cell Biology, Columbia University Irving Medical Center.

Refractory celiac disease type II (RCD II), also referred to as "cryptic" enteropathy-associated T-cell lymphoma (EATL) or "intraepithelial T-cell lymphoma," is a rare clonal lymphoproliferative disorder that arises from innate intraepithelial lymphocytes. RCD II has a poor prognosis and frequently evolves to EATL. The pathogenesis of RCD II is not well understood and data regarding the immunophenotypic spectrum of this disease and underlying genetic alterations are limited. Read More

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Germline Pathogenic Variants in the Ataxia Telangiectasia Mutated () Gene are Associated with High and Moderate Risks for Multiple Cancers.

Cancer Prev Res (Phila) 2021 Apr 28;14(4):433-440. Epub 2021 Jan 28.

Stanford University, Stanford, California.

Pathogenic variants (PVs) in are relatively common, but the scope and magnitude of risk remains uncertain. This study aimed to estimate PV cancer risks independent of family cancer history. This analysis included patients referred for hereditary cancer testing with a multi-gene panel ( = 627,742). Read More

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Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications.

Sci Rep 2021 01 15;11(1):1526. Epub 2021 Jan 15.

Department of Genetics, Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain.

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Read More

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January 2021

Pathogenicity assessment of variants for breast cancer susceptibility genes based on BRCAness of tumor sample.

Cancer Sci 2021 Mar 2;112(3):1310-1319. Epub 2021 Feb 2.

Division of Cancer Genomics, Cancer Institute, Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan.

Genes involved in the homologous recombination repair pathway-as exemplified by BRCA1, BRCA2, PALB2, ATM, and CHEK2-are frequently associated with hereditary breast and ovarian cancer syndrome. Germline mutations in the loci of these genes with loss of heterozygosity or additional somatic truncation at the WT allele lead to the development of breast cancers with characteristic clinicopathological features and prominent genomic features of homologous recombination deficiency, otherwise referred to as "BRCAness." Although clinical genetic testing for these and other genes has increased the chances of identifying pathogenic variants, there has also been an increase in the prevalence of variants of uncertain significance, which poses a challenge to patient care because of the difficulties associated with making further clinical decisions. Read More

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Six Novel ATM Gene Variants in Sri Lankan Patients with Ataxia Telangiectasia.

Case Rep Genet 2020 9;2020:6630300. Epub 2020 Dec 9.

Human Genetics Unit, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.

Introduction: Ataxia telangiectasia is a rare genetic condition with an estimated prevalence of 1 in 40,000-100,000 live births. This condition predominantly affects the nervous and immune systems. It is characterized by progressive ataxia beginning from early childhood. Read More

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December 2020