98,353 results match your criteria genetic deletion

Long-read nanopore sequencing enables accurate confirmation of a recurrent PMS2 insertion-deletion variant located in a region of complex genomic architecture.

Cancer Genet 2021 May 28;256-257:122-126. Epub 2021 May 28.

Leeds Institute of Medical Research, University of Leeds, St. James's University Hospital, Leeds LS9 7TF, United Kingdom; The Clinical Genetics Department, Chapel Allerton Hospital, Leeds LS7 4SA, United Kingdom.

Targeted next generation sequencing (NGS) is the predominant methodology for the molecular genetic diagnosis of inherited conditions. In many laboratories, NGS-identified variants are routinely validated using a different method, to minimize the risk of a false-positive diagnosis. This can be particularly important when pathogenic variants are located in complex genomic regions. Read More

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Variant-genetic and transcript-expression analysis showed a role for the chemokine-receptor CCR5 in COVID-19 severity.

Int Immunopharmacol 2021 Jun 2;98:107825. Epub 2021 Jun 2.

Genética Molecular, Hospital Universitario Central Asturias, Oviedo, Spain; Instituto de Investigación Sanitaria del Principado deAsturias, ISPA, Oviedo, Spain; Universidad de Oviedo, Oviedo, Spain; Red de Investigación Renal (REDINREN), Madrid, Spain. Electronic address:

The chemokine receptor CCR5 has been implicated in COVID-19. CCR5 and its ligands are overexpressed in patients. The pharmacological targeting of CCR5 would improve the COVID-19 severity. Read More

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Resilience and quality of life in young adults with a 22q11.2 deletion syndrome: a patient's perspective.

Eur Child Adolesc Psychiatry 2021 Jun 11. Epub 2021 Jun 11.

Department of Human Genetics, KU Leuven, Leuven, Belgium.

In the transition period between adolescence and young adulthood, individuals with 22q11.2DS are at an increased risk of developing severe psychiatric disorders. Various studies have focused on detecting risk factors, but until now protective factors are still understudied in 22q11. Read More

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A five amino acids deletion in NKCC2 of C57BL/6 mice affects analysis of NKCC2 phosphorylation but does not impact kidney function.

Acta Physiol (Oxf) 2021 Jun 11:e13705. Epub 2021 Jun 11.

Institute of Anatomy, University of Zurich, Switzerland.

Aim: The phosphorylation level of the furosemide-sensitive Na -K -2Cl cotransporter (NKCC2) in the thick ascending limb (TAL) is used as a surrogate marker for NKCC2 activation and TAL function. However, in mice, analyses of NKCC2 phosphorylation with antibodies against phosphorylated threonines 96 and 101 (anti-pT96/pT101) give inconsistent results. We aimed (i) to elucidate these inconsistencies and (ii) to develop a phosphoform-specific antibody that ensures reliable detection of NKCC2 phosphorylation in mice. Read More

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SAA1/TLR2 axis directs chemotactic migration of hepatic stellate cells responding to injury.

iScience 2021 May 29;24(5):102483. Epub 2021 Apr 29.

Institute of Public Health, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Avenue, Science Park, Guangzhou, Guangdong 510530, China.

Hepatic stellate cells (HSCs) are crucial for liver injury repair and cirrhosis. However, the mechanism of chemotactic recruitment of HSCs into injury loci is still largely unknown. Here, we demonstrate that serum amyloid A1 (SAA1) acts as a chemokine recruiting HSCs toward injury loci signaling via TLR2, a finding proven by gene manipulation studies in cell and mice models. Read More

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The Adenylate Cyclase, CyaB, Is Important for Virulence Factor Production and Mammalian Infection.

Front Microbiol 2021 25;12:676192. Epub 2021 May 25.

Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX, United States.

, the causative agent of Lyme disease, traverses through vastly distinct environments between the tick vector and the multiple phases of the mammalian infection that requires genetic adaptation for the progression of pathogenesis. Borrelial gene expression is highly responsive to changes in specific environmental signals that initiate the RpoS regulon for mammalian adaptation, but the mechanism(s) for direct detection of environmental cues has yet to be identified. Secondary messenger cyclic adenosine monophosphate (cAMP) produced by adenylate cyclase is responsive to environmental signals, such as carbon source and pH, in many bacterial pathogens to promote virulence by altering gene regulation. Read More

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Deletion of the clock gene Period2 (Per2) in glial cells alters mood-related behavior in mice.

Sci Rep 2021 Jun 10;11(1):12242. Epub 2021 Jun 10.

Department of Biology, Faculty of Science and Medicine, University of Fribourg, 1700, Fribourg, Switzerland.

The circadian clock regulates many biochemical and physiological pathways, and lack of clock genes, such as Period (Per) 2, affects not only circadian activity rhythms, but can also modulate feeding and mood-related behaviors. However, it is not known how cell-type specific expression of Per2 contributes to these behaviors. In this study, we find that Per2 in glial cells is important for balancing mood-related behaviors, without affecting circadian activity parameters. Read More

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HGK promotes metastatic dissemination in prostate cancer.

Sci Rep 2021 Jun 10;11(1):12287. Epub 2021 Jun 10.

Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia , Universidad Complutense de Madrid, Ciudad Universitaria , Madrid, Spain.

Metastasis is the process of cancer cell dissemination from primary tumors to different organs being the bone the preferred site for metastatic homing of prostate cancer (PCa) cells. Prostate tumorigenesis is a multi-stage process that ultimately tends to advance to become metastatic PCa. Once PCa patients develop skeletal metastases, they eventually succumb to the disease. Read More

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Impairment of a distinct cancer-associated fibroblast population limits tumour growth and metastasis.

Nat Commun 2021 06 10;12(1):3516. Epub 2021 Jun 10.

The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.

Profiling studies have revealed considerable phenotypic heterogeneity in cancer-associated fibroblasts (CAFs) present within the tumour microenvironment, however, functional characterisation of different CAF subsets is hampered by the lack of specific markers defining these populations. Here we show that genetic deletion of the Endo180 (MRC2) receptor, predominantly expressed by a population of matrix-remodelling CAFs, profoundly limits tumour growth and metastasis; effects that can be recapitulated in 3D co-culture assays. This impairment results from a CAF-intrinsic contractility defect and reduced CAF viability, which coupled with the lack of phenotype in the normal mouse, demonstrates that upregulated Endo180 expression by a specific, potentially targetable CAF subset is required to generate a supportive tumour microenvironment. Read More

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Necroptosis protects against exacerbation of acute pancreatitis.

Cell Death Dis 2021 Jun 10;12(6):601. Epub 2021 Jun 10.

Department of Immunology and Parasitology, Graduate School of Medicine, Tokushima University, Tokushima, Japan.

The sensing of various extrinsic stimuli triggers the receptor-interacting protein kinase-3 (RIPK3)-mediated signaling pathway, which leads to mixed-lineage kinase-like (MLKL) phosphorylation followed by necroptosis. Although necroptosis is a form of cell death and is involved in inflammatory conditions, the roles of necroptosis in acute pancreatitis (AP) remain unclear. In the current study, we administered caerulein to Ripk3- or Mlkl-deficient mice (Ripk3 or Mlkl mice, respectively) and assessed the roles of necroptosis in AP. Read More

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Emerging mutant populations of Listeria monocytogenes EGD-e under selective pressure of Thymbra capitata essential oil question its use in food preservation.

Food Res Int 2021 Jul 12;145:110403. Epub 2021 May 12.

Departamento de Producción Animal y Ciencia de los Alimentos, Facultad de Veterinaria, Instituto Agroalimentario de Aragón-IA2 (Universidad de Zaragoza-CITA), Zaragoza, Spain. Electronic address:

Due to their excellent antimicrobial properties, essential oils (EO) have been proposed as potential preservatives for certain kinds of foods, such as dairy products. However, the occurrence of pathogenic populations that are resistant to EOs could pose a health risk. This report seeks to assess the emergence of resistant populations in Listeria monocytogenes EGD-e growth at 37 °C under selective pressure of Thymbra capitata EO (TCO), to characterise their resistance in laboratory media, and to identify their genotypic changes, as well as to evaluate the resistance in skimmed milk. Read More

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Longitudinal Psychiatric and Developmental Outcomes in 22q11.2 Deletion Syndrome: A Systematic Review.

J Dev Behav Pediatr 2021 Jun-Jul 01;42(5):415-427

Department of Psychology, Syracuse University, Syracuse, NY.

Objective: 22q11.2 deletion syndrome (22q11DS) is a common genetic deletion syndrome associated with psychiatric disorders and developmental delays. A significant amount of 22q11DS research literature is published annually; here, we focus exclusively on longitudinal data that have been published in the past 5 years regarding psychiatric disorders and/or cognitive and social development. Read More

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Severe speech impairment is a distinguishing feature of FOXP1-related disorder.

Dev Med Child Neurol 2021 Jun 9. Epub 2021 Jun 9.

Murdoch Children's Research Institute, Parkville, VIC, Australia.

Aim: To delineate the speech and language phenotype of a cohort of individuals with FOXP1-related disorder.

Method: We administered a standardized test battery to examine speech and oral motor function, receptive and expressive language, non-verbal cognition, and adaptive behaviour. Clinical history and cognitive assessments were analysed together with speech and language findings. Read More

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Genetic Variation in Two Populations From Ecuador Highlands-Extensive Copy-Number Variation, Distinctive Distribution of Functional Polymorphisms, and a Novel, Locally Common, Chimeric (CD16B/A) Gene.

Front Immunol 2021 24;12:615645. Epub 2021 May 24.

Immunogenetics & Histocompatibility Lab, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Majadahonda, Spain.

Fcγ receptors (FcγR), cell-surface glycoproteins that bind antigen-IgG complexes, control both humoral and cellular immune responses. The locus on chromosome 1q23.3 comprises five homologous genes encoding low-affinity FcγRII and FcγRIII, and displays functionally relevant polymorphism that impacts on human health. Read More

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Cardiac Involvement in Facioscapulohumeral Muscular Dystrophy (FSHD).

Front Neurol 2021 24;12:668180. Epub 2021 May 24.

Department of Neurology, Mayo Clinic, Rochester, MN, United States.

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies and predominantly affects facial and shoulder girdle muscles. Previous case reports and cohort studies identified minor cardiac abnormalities in FSHD patients, but their nature and frequency remain incompletely characterized. We reviewed cardiac, neurological and genetic findings of 104 patients with genetically confirmed FSHD. Read More

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GluN2D NMDA Receptors Gate Fear Extinction Learning and Interneuron Plasticity.

Front Synaptic Neurosci 2021 24;13:681068. Epub 2021 May 24.

Department of Cell Biology and Anatomy, LSU Health Sciences Center New Orleans, New Orleans, LA, United States.

The cerebellum is critically involved in the formation of associative fear memory and in subsequent extinction learning. Fear conditioning is associated with a long-term potentiation at both excitatory and inhibitory synapses onto Purkinje cells. We therefore tested whether fear conditioning unmasks novel forms of synaptic plasticity, which enable subsequent extinction learning to reset cerebellar circuitry. Read More

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Redefining IL11 as a regeneration-limiting hepatotoxin and therapeutic target in acetaminophen-induced liver injury.

Sci Transl Med 2021 Jun;13(597)

Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore 169857, Singapore.

Acetaminophen (-acetyl--aminophenol; APAP) toxicity is a common cause of liver damage. In the mouse model of APAP-induced liver injury (AILI), interleukin 11 (IL11) is highly up-regulated and administration of recombinant human IL11 (rhIL11) has been shown to be protective. Here, we demonstrate that the beneficial effect of rhIL11 in the mouse model of AILI is due to its inhibition of endogenous mouse IL11 activity. Read More

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An MD2-perturbing peptide has therapeutic effects in rodent and rhesus monkey models of stroke.

Sci Transl Med 2021 Jun;13(597)

Translational Research Institute of Brain and Brain-Like Intelligence and Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, Tongji University School of Medicine, Shanghai 200434, China.

Studies have failed to translate more than 1000 experimental treatments from bench to bedside, leaving stroke as the second leading cause of death in the world. Thrombolysis within 4.5 hours is the recommended therapy for stroke and cannot be performed until neuroimaging is used to distinguish ischemic stroke from hemorrhagic stroke. Read More

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Genomic and Phenotypic Analysis of COVID-19-Associated Pulmonary Aspergillosis Isolates of Aspergillus fumigatus.

Microbiol Spectr 2021 Jun 9:e0001021. Epub 2021 Jun 9.

Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, USA.

The ongoing global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19), first described in Wuhan, China. A subset of COVID-19 patients has been reported to have acquired secondary infections by microbial pathogens, such as opportunistic fungal pathogens from the genus Aspergillus. To gain insight into COVID-19-associated pulmonary aspergillosis (CAPA), we analyzed the genomes and characterized the phenotypic profiles of four CAPA isolates of Aspergillus fumigatus obtained from patients treated in the area of North Rhine-Westphalia, Germany. Read More

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Sweet tooth: DNA profiling of a cranium from an isolated retained root fragment.

J Forensic Sci 2021 Jun 9. Epub 2021 Jun 9.

Department of Public Health Sciences and Pediatrics, University of Turin, Turin, Italy.

Sampling of healthy multi-rooted teeth is recommended for the genetic identification of human skeletal remains. However, this may not always be possible, as in the reported case consisting of an isolated human cranium found in an aggregate crushing and processing plant in Piedmont, Northwest Italy. The cranium displayed significant weathering, suggesting a post-mortem interval of several years, and was edentulous with the exception of the apical root fragment of the upper left canine, consequence of an antemortem horizontal fracture. Read More

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[Analysis of Gene Deficiency Types of Thalassemia in Lingui District of Guilin City].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Jun;29(3):860-864

Department of Laboratorial Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin 541199, Guangxi Zhuang Autonomous Region, China,E-mail:

Objective: To analyze the gene defect types and distribution characteristics of α- and β-thalassemia in Lingui District of Guilin City, Guangxi, so as to provide scientific basis for genetic consultation and prevention measures.

Methods: A total of 6 496 suspected cases for screening the thalassemia during physical examination, premarital examination, pregnancy examination and hospitalization in the Second Affiliated Hospital of Guilin Medical University from May 2016 to October 2019 were analyzed. Gap-PCR, PCR-RDB and DNA sequencing techniques were used to detect the types and constituent ratios of gene defects in α- and β-thalassemia positive cases. Read More

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[Clinical Analysis of Patients with MGUS, Primary Light Chain Amyloidosis, Multiple Myeloma or Multiple Myeloma with Concurrent Amyloidosis].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Jun;29(3):812-818

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China,E-mail:

Objective: To summarize and compare the clinical baseline characteristics of patients with monoclonal gammopathy of undetermined significance (MGUS), primary light chain amyloidosis (pAL), multiple myeloma (MM), or MM with concurrent amyloidosis, especially the differences in cytogenetic abnormalities.

Methods: The clinical data of 15 cases of MGUS, 34 cases of pAL, 842 cases of MM and 23 cases of MM with concurrent amyloidosis were analyzed and compared retrospectively.

Results: Cytogenetic statistics showed that the incidence of t (11; 14) in the four groups (MGUS vs pAL vs MM vs MM with concurrent amyloidosis) was 0%, 33. Read More

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IRE1α-mediated monounsaturated fatty acid synthesis drives B cell differentiation and lupus-like autoimmune disease.

Arthritis Rheumatol 2021 Jun 8. Epub 2021 Jun 8.

Department of Pathology, Northwestern University Feinberg School of Medicine, 303 E. Chicago Ave, Chicago, IL, 60611, USA.

Objectives: This study is to explore the molecular mechanisms underlying how the lipid metabolic dysregulation is associated with systemic lupus erythematosus (SLE) pathogenesis.

Methods: B cells in peripheral blood from lupus patients and healthy controls were used for lipid bodipy analysis. B-cell specific IRE1α and SCD1 knockout mice were employed for studying the influence of IRE1α-SCD1/2 pathway on B-cell differentiation and auto-antibody production. Read More

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Supramolecular Nanosubstrate-Mediated Delivery for CRISPR/Cas9 Gene Disruption and Deletion.

Small 2021 Jun 8:e2100546. Epub 2021 Jun 8.

Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, California NanoSystems Institute (CNSI), Crump Institute for Molecular Imaging (CIMI), University of California, Los Angeles, Los Angeles, CA, 90095, USA.

The clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR/Cas9) is an efficient and precise gene-editing technology that offers a versatile solution for establishing treatments directed at genetic diseases. Currently, CRISPR/Cas9 delivery into cells relies primarily on viral vectors, which suffer from limitations in packaging capacity and safety concerns. These issues with a nonviral delivery strategy are addressed, where Cas9•sgRNA ribonucleoprotein (RNP) complexes can be encapsulated into supramolecular nanoparticles (SMNP) to form RNP⊂SMNPs, which can then be delivered into targeted cells via supramolecular nanosubstrate-mediated delivery. Read More

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The Oral Health of Patients with DiGeorge Syndrome (22q11) Microdeletion: A Case Report.

Appl Clin Genet 2021 1;14:267-277. Epub 2021 Jun 1.

Congenital Abnormalities and Rare Disease Centre (CIACER), Cali, Colombia.

Background: DiGeorge syndrome (DG) is a genetic disorder associated with 22q11 deletion. It involves various phenotypes, including craniofacial abnormalities, congenital heart disorders, endocrine dysfunction, cognitive deficits, and psychiatric disorders. Cases commonly involve multiple anomalies. Read More

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Familial exudative vitreoretinopathy with mutation without signs of Loeys-Dietz syndrome.

Ophthalmic Genet 2021 Jun 9:1-4. Epub 2021 Jun 9.

Department of Ophthalmology, University of Occupational and Environmental Health, Kitakyushu, Japan.

: Familial exudative vitreoretinopathy (FEVR) is an inherited retinal disorder with high genetic heterogeneity, and it is characterized by a defect in the development of the retinal vascular system. Loeys-Dietz syndrome (LDS) is an autosomal dominant systemic connective tissue disorder that is caused by mutations in the genes related to transforming growth factor signaling systems including the gene. Two earlier studies reported that patients with LDS from mutations in the gene were associated with FEVR-like retinal phenotype. Read More

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[Clinical features of epilepsy in children with IRF2BPL gene variation].

Zhonghua Er Ke Za Zhi 2021 Jun;59(6):506-510

Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.

To summarize the genotype and phenotype of epilepsy in patients with interferon regulatory factor 2 binding protein-like (IRF2BPL) gene variants. Data of 6 epilepsy patients with IRF2BPL gene variants seen from May 2017 to September 2020 in the Department of Pediatrics of Peking University First Hospital were retrospectively collected. The clinical characteristics and genetic test results were analyzed. Read More

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[Analysis of the clinical perinatal characteristics of 226 patients with Prader-Willi syndrome in China].

Zhonghua Er Ke Za Zhi 2021 Jun;59(6):466-470

Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.

To enhance the early recognition of Prader-Willi syndrome by summarizing the clinical characteristics of Prader-Willi syndrome (PWS) during perinatal period. Through a nationwide cross-sectional study in the Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences,226 children diagnosed as PWS by molecular genetics were recruited from September 2019 to March 2020. Clinical data including fetuses Age, birth weight, fetal movement, fetal position, amniotic fluid, mode of bith, crying, muscle tension, feeding, and cryptorchidism were collected to analyze the clinical characteristics of Chinese PWS patients in the perinatal period, and according to the mode of birty, birth weight and genotypes to perform subgroup analysis. Read More

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Hereditary factor V deficiency from heterozygous mutations with a novel variant p.Pro798Leufs*13 in the F5 gene.

Blood Coagul Fibrinolysis 2021 Jun 7. Epub 2021 Jun 7.

Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

To explore the causative mutation for autosomal recessive inheritance factor V (FV) deficiency in a Chinese family. Relative coagulation indexes and the FV antigen were tested by the one-stage clotting method and ELISA, respectively. At the same time, the calibrated automated thrombogram (CAT) was used to analyze the mutant protein function. Read More

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Dysfunction of the limbal epithelial stem cell niche in aniridia-associated keratopathy.

Ocul Surf 2021 Jun 5. Epub 2021 Jun 5.

Department of Ophthalmology, Saarland University Medical Center, Homburg/Saar, Germany.

Purpose: Abnormalities in the limbal niche microenvironment have been suggested to be causally involved in aniridia-associated keratopathy (AAK), but histological analyses on the limbal structure and composition in AAK are lacking. Here, we investigated morphologic and molecular alterations of the limbal epithelial stem cell niche in human congenital aniridia.

Methods: The blind, buphthalmic and painful left eye of a 16-year old girl with congenital aniridia and juvenile glaucoma had to be enucleated because of uncontrolled intraocular pressure. Read More

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