71,507 results match your criteria mutations result

Whole exome sequencing improves mutation detection in Hailey-Hailey disease.

J Dermatol 2021 Apr 20. Epub 2021 Apr 20.

Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.

Hailey-Hailey disease (HHD) is an autosomal dominant monogenic disease that is defective in the ATP2C1 gene. In previous studies, Sanger sequencing was the main method applied to detect mutations in HHD patients, and no mutations in the ATP2C1 gene were found in 12-55% of those reported. The aim of our study was to carry out whole exome sequencing (WES) for the HHD patients in whom efforts to identify mutations by Sanger sequencing had failed, and to find a new pathogenic gene. Read More

View Article and Full-Text PDF

The Enzymes of the Rifamycin Antibiotic Resistome.

Acc Chem Res 2021 Apr 20. Epub 2021 Apr 20.

M.G. DeGroote Institute for Infectious Disease Research, David Braley Center for Antibiotic Discovery, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8S 3Z5, Canada.

ConspectusRifamycin antibiotics include the WHO essential medicines rifampin, rifabutin, and rifapentine. These are semisynthetic derivatives of the natural product rifamycins, originally isolated from the soil bacterium . These antibiotics are primarily used to treat mycobacterial infections, including tuberculosis. Read More

View Article and Full-Text PDF

CanDriS: posterior profiling of cancer-driving sites based on two-component evolutionary model.

Brief Bioinform 2021 Apr 20. Epub 2021 Apr 20.

Department of Genetics, Development and Cell Biology, Iowa State University, Ames, 12 Iowa 50011, USA.

Current cancer genomics databases have accumulated millions of somatic mutations that remain to be further explored. Due to the over-excess mutations unrelated to cancer, the great challenge is to identify somatic mutations that are cancer-driven. Under the notion that carcinogenesis is a form of somatic-cell evolution, we developed a two-component mixture model: while the ground component corresponds to passenger mutations, the rapidly evolving component corresponds to driver mutations. Read More

View Article and Full-Text PDF

Role of the SOS Response in the Generation of Antibiotic Resistance In Vivo.

Antimicrob Agents Chemother 2021 Apr 19. Epub 2021 Apr 19.

Department of Biochemistry, University at Buffalo, Buffalo, NY, USA.

The SOS response to DNA damage is a conserved stress response in Gram-negative and Gram-positive bacteria. Although this pathway has been studied for years, its relevance is still not familiar to many working in the fields of clinical antibiotic resistance and stewardship. In some conditions, the SOS response favors DNA repair and preserves the genetic integrity of the organism. Read More

View Article and Full-Text PDF

Rare deleterious mutations of HNRNP genes result in shared neurodevelopmental disorders.

Madelyn A Gillentine Tianyun Wang Kendra Hoekzema Jill Rosenfeld Pengfei Liu Hui Guo Chang N Kim Bert B A De Vries Lisenka E L M Vissers Magnus Nordenskjold Malin Kvarnung Anna Lindstrand Ann Nordgren Jozef Gecz Maria Iascone Anna Cereda Agnese Scatigno Silvia Maitz Ginevra Zanni Enrico Bertini Christiane Zweier Sarah Schuhmann Antje Wiesener Micah Pepper Heena Panjwani Erin Torti Farida Abid Irina Anselm Siddharth Srivastava Paldeep Atwal Carlos A Bacino Gifty Bhat Katherine Cobian Lynne M Bird Jennifer Friedman Meredith S Wright Bert Callewaert Florence Petit Sophie Mathieu Alexandra Afenjar Celenie K Christensen Kerry M White Orly Elpeleg Itai Berger Edward J Espineli Christina Fagerberg Charlotte Brasch-Andersen Lars Kjærsgaard Hansen Timothy Feyma Susan Hughes Isabelle Thiffault Bonnie Sullivan Shuang Yan Kory Keller Boris Keren Cyril Mignot Frank Kooy Marije Meuwissen Alice Basinger Mary Kukolich Meredith Philips Lucia Ortega Margaret Drummond-Borg Mathilde Lauridsen Kristina Sorensen Anna Lehman Elena Lopez-Rangel Paul Levy Davor Lessel Timothy Lotze Suneeta Madan-Khetarpal Jessica Sebastian Jodie Vento Divya Vats L Manace Benman Shane Mckee Ghayda M Mirzaa Candace Muss John Pappas Hilde Peeters Corrado Romano Maurizio Elia Ornella Galesi Marleen E H Simon Koen L I van Gassen Kara Simpson Robert Stratton Sabeen Syed Julien Thevenon Irene Valenzuela Palafoll Antonio Vitobello Marie Bournez Laurence Faivre Kun Xia Rachel K Earl Tomasz Nowakowski Raphael A Bernier Evan E Eichler

Genome Med 2021 Apr 19;13(1):63. Epub 2021 Apr 19.

Department of Genome Sciences, University of Washington School of Medicine, 3720 15th Ave NE S413A, Box 355065, Seattle, WA, 981095-5065, USA.

Background: With the increasing number of genomic sequencing studies, hundreds of genes have been implicated in neurodevelopmental disorders (NDDs). The rate of gene discovery far outpaces our understanding of genotype-phenotype correlations, with clinical characterization remaining a bottleneck for understanding NDDs. Most disease-associated Mendelian genes are members of gene families, and we hypothesize that those with related molecular function share clinical presentations. Read More

View Article and Full-Text PDF

The epidermal surface of the maize root tip: II. Abnormalities in a mutant which grows crookedly through soil.

New Phytol 1993 Dec;125(4):801-811

Department of Biology, Carleton University, Ottawa, Canada K1S 5B6.

The mutation Ageotropic (Agt) results in defective development of the surface pellicle which overlies the young epidermal cells of mesocotyl and nodal roots of maize. In roots of plants of the parent, cv. Kys, pellicle development is normal. Read More

View Article and Full-Text PDF
December 1993

Proline metabolism and transport in retinal health and disease.

Amino Acids 2021 Apr 19. Epub 2021 Apr 19.

Department of Ophthalmology, University of Washington, Seattle, WA, 98109, USA.

The retina is one of the most energy-demanding tissues in the human body. Photoreceptors in the outer retina rely on nutrient support from the neighboring retinal pigment epithelium (RPE), a monolayer of epithelial cells that separate the retina and choroidal blood supply. RPE dysfunction or cell death can result in photoreceptor degeneration, leading to blindness in retinal degenerative diseases including some inherited retinal degenerations and age-related macular degeneration (AMD). Read More

View Article and Full-Text PDF

Population bottlenecks strongly affect the evolutionary dynamics of antibiotic persistence.

Mol Biol Evol 2021 Apr 19. Epub 2021 Apr 19.

VIB Center for Microbiology, Flanders Institute for Biotechnology, Leuven, Belgium.

Bacterial persistence is a potential cause of antibiotic therapy failure. Antibiotic-tolerant persisters originate from phenotypic differentiation within a susceptible population, occurring with a frequency that can be altered by mutations. Recent studies have proven that persistence is a highly evolvable trait and, consequently, an important evolutionary strategy of bacterial populations to adapt to high-dose antibiotic therapy. Read More

View Article and Full-Text PDF

Visualizing Ocular Morphogenesis by Lightsheet Microscopy using rx3:GFP Transgenic Zebrafish.

J Vis Exp 2021 Apr 5(170). Epub 2021 Apr 5.

Department of Biology, University of Kentucky;

Vertebrate eye development is a complex process that begins near the end of embryo gastrulation and requires the precise coordination of cell migration, proliferation, and differentiation. Time-lapse imagining offers unique insight to the behavior of cells during eye development because it allows us to visualize oculogenesis in vivo. Zebrafish are an excellent model to visualize this process due to their highly conserved vertebrate eye and their ability to develop rapidly and externally while remaining optically transparent. Read More

View Article and Full-Text PDF

Ghrelin hormone might have a potential role in amelogenesis.

Int J Clin Pract 2021 Apr 19:e14223. Epub 2021 Apr 19.

Istanbul University-Cerrahpasa, Biochemistry, Turkey.

Aims: Amelogenesis Imperfecta and Generalized Enamel Hypoplasia are developmental dental anomalies that affect dental enamel. While Amelogenesis imperfecta results from various gene mutations, the exact underlying mechanisms of the etiopathogenesis of both remain unclear. This study aims to evaluate Ghrelin hormone levels in children with generalized enamel hypoplasia to establish whether Ghrelin might have a potential role in enamel hypoplasia's etiology. Read More

View Article and Full-Text PDF

Exploring the Roles of HERC2 and the NEDD4L HECT E3 Ubiquitin Ligase Subfamily in p53 Signaling and the DNA Damage Response.

Front Oncol 2021 31;11:659049. Epub 2021 Mar 31.

Gustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA, United States.

Cellular homeostasis is governed by the precise expression of genes that control the translation, localization, and termination of proteins. Oftentimes, environmental and biological factors can introduce mutations into the genetic framework of cells during their growth and division, and these genetic abnormalities can result in malignant transformations caused by protein malfunction. For example, p53 is a prominent tumor suppressor protein that is capable of undergoing more than 300 posttranslational modifications (PTMs) and is involved with controlling apoptotic signaling, transcription, and the DNA damage response (DDR). Read More

View Article and Full-Text PDF

Case Report: Partial Uniparental Disomy Unmasks a Novel Recessive Mutation in the Gene in a Patient With a Severe Phenotype of Chédiak-Higashi Syndrome.

Front Immunol 2021 31;12:625591. Epub 2021 Mar 31.

Department of Hematology, Hospital Universitario y Politécnico La Fe, Barcelona, Spain.

Chédiak-Higashi syndrome (CHS) is a rare autosomal recessive (AR) immune disorder that has usually been associated to missense, nonsense or indels mutations in the gene. In this study, we describe for the first time the case of a CHS patient carrying a homozygous mutation in the gene inherited as a result of a partial uniparental isodisomy (UPiD) of maternal origin. Sanger sequencing of the cDNA and single nucleotide polymorphism (SNP)-arrays were performed to identify the causative mutation and to explain the molecular mechanism of inheritance, respectively. Read More

View Article and Full-Text PDF

Resistance to Thyroid Hormone Beta: A Focused Review.

Front Endocrinol (Lausanne) 2021 31;12:656551. Epub 2021 Mar 31.

Departments of Medicine, Pediatrics and Committee on Genetics, The University of Chicago, Chicago, IL, United States.

Resistance to thyroid hormone (RTH) is a clinical syndrome defined by impaired sensitivity to thyroid hormone (TH) and its more common form is caused by mutations in the gene, termed RTHβ. The characteristic biochemical profile is that of elevated serum TH levels in absence of thyrotropin suppression. Although most individuals are considered clinically euthyroid, there is variability in phenotypic manifestation among individuals harboring different mutations and among tissue types in the same individual due in part to differential expression of the mutant TRβ protein. Read More

View Article and Full-Text PDF

Homozygous missense mutation in UQCRC2 associated with severe encephalomyopathy, mitochondrial complex III assembly defect and activation of mitochondrial protein quality control.

Biochim Biophys Acta Mol Basis Dis 2021 Apr 15:166147. Epub 2021 Apr 15.

Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic. Electronic address:

The mitochondrial respiratory chain (MRC) complex III (CIII) associates with complexes I and IV (CI and CIV) into supercomplexes. We identified a novel homozygous missense mutation (c.665G>C; p. Read More

View Article and Full-Text PDF

A SNP of HD-ZIP I transcription factor leads to distortion of trichome morphology in cucumber (Cucumis sativus L.).

BMC Plant Biol 2021 Apr 16;21(1):182. Epub 2021 Apr 16.

School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, China.

Background: Trichomes are excellent model systems for the analysis of cell differentiation and play essential roles in plant protection. From cucumber inbred line 'WD1', we identified an EMS-induced trichome abnormally developing mutant, nps, which exhibited smaller, denser and no pyramid-shaped head trichomes.

Results: Using F and BC populations constructed from a cross between nps and '9930', the genetic analysis showed that the nps trait is controlled by a single recessive nuclear gene. Read More

View Article and Full-Text PDF

Role of thermal fluctuations in biological copying mechanisms.

Phys Rev E 2021 Mar;103(3-1):032110

Max Planck Institute for the Physics of Complex Systems, Nöthnitzer Strasse 38, 01187 Dresden, Germany.

During transcription, translation, or self-replication of DNA or RNA, information is transferred to the newly formed species from its predecessor. These processes can be interpreted as (generalized) biological copying mechanism as the new biological entities like DNA, RNA, or proteins are representing the information of their parent bodies uniquely. The accuracy of these copying processes is essential, since errors in the copied code can reduce the functionality of the next generation. Read More

View Article and Full-Text PDF

Evidence for frequent concurrent DCUN1D1, FGFR1, BCL9 gene copy number amplification in squamous cell lung cancer.

Pathol Res Pract 2021 Mar 24;221:153412. Epub 2021 Mar 24.

1(st) Department of Pathology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias str., 11527, Goudi, Athens, Greece. Electronic address:

Non-small cell lung cancer (NSCLC) targeted therapies are mostly based on activating mutations and rearrangements which are rare events in Lung Squamous Cell Carcinomas (LUSC). Recently advances in immunotherapy have improved the therapeutic repository for LUSC, but there is still an urgent need for novel targets and biomarkers. We examined 73 cases of LUSC for relative copy number amplification of DCUN1D1, BCL9, FGFR1 and ERBB2 genes and searched for correlations with molecular alterations and clinicopathological characteristics. Read More

View Article and Full-Text PDF

Losing balance: kainate receptors and psychiatric disorders comorbidities.

Neuropharmacology 2021 Apr 13:108558. Epub 2021 Apr 13.

Instituto de Neurociencias CSIC-UMH, 03550, San Juan de Alicante, Spain. Electronic address:

Cognition and behavior are tightly linked to synaptic function. A growing body of evidence suggests that aberrant neurotransmission, caused by changes in synaptic protein expression levels, may be a major cause underlying different brain disorders. These changes in expression result in abnormal synaptic organization or function, leading to impaired neurotransmission and unbalanced circuit operations. Read More

View Article and Full-Text PDF

A complement factor H homolog, heparan sulfation, and syndecan maintain inversin compartment boundaries in cilia.

Proc Natl Acad Sci U S A 2021 Apr;118(16)

Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, University of Maryland, Baltimore, MD 21201;

Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly. Canonical disease models suggest that defective interactions between complement factor H (CFH) and cell surface heparan sulfate (HS) result in increased alternative complement pathway activity, cytolytic damage, and tissue inflammation in the retina. Although these factors are thought to contribute to increased disease risk, multiple studies indicate that noncanonical mechanisms that result from defective CFH and HS interaction may contribute to the progression of AMD as well. Read More

View Article and Full-Text PDF

Association of IL-10 (- 1082 A/G) and IL-6 (- 174 G/C) gene polymorphism with type 2 diabetes mellitus in Ethiopia population.

BMC Endocr Disord 2021 Apr 15;21(1):70. Epub 2021 Apr 15.

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

Background: Interleukin (IL)-6 and IL-10 are the most important cytokine with pro and anti-inflammatory activities, respectively. Dysregulation of IL-6 and IL-10 are associated with increased risk of developing Type 2 Diabetes Mellitus (T2DM). Despite this, a fundamental understanding of both cytokine gene polymorphisms with its expression is critical in understanding of cellular mechanism of insulin resistance as well as T2DM intervention. Read More

View Article and Full-Text PDF

The hydrogen bonding network involved Arg59 in human protoporphyrinogen IX oxidase is essential for enzyme activity.

Biochem Biophys Res Commun 2021 Apr 12;557:20-25. Epub 2021 Apr 12.

State Key Laboratory of Elemento-Organic Chemistry and Department of Chemical Biology, National Pesticide Engineering Research Center (Tianjin), Nankai University, 94 Weijin Road, Tianjin, 300071, China. Electronic address:

Protoporphyrinogen IX oxidase (PPO) is the last common enzyme in chlorophyll and heme biosynthesis pathways. In human, point mutations on PPO are responsible for the dominantly inherited disorder disease, Variegate Porphyria (VP). Of the VP-causing mutation site, the Arg59 is by far the most prevalent VP mutation residue identified. Read More

View Article and Full-Text PDF

Differential diagnosis of vitamin D-related hypercalcemia using serum vitamin D metabolite profiling.

J Bone Miner Res 2021 Apr 15. Epub 2021 Apr 15.

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada, K7L3N6.

Genetic causes of vitamin D-related hypercalcemia are known to involve mutation of 25-hydroxyvitamin D-24-hydroxylase CYP24A1 or the sodium phosphate co-transporter SLC34A1; which result in excessive 1,25-(OH) D hormonal action. However, at least 20% of idiopathic hypercalcemia (IH) cases remain unresolved. In this case-control study, we used precision vitamin D metabolite profiling based on LC-MS/MS of an expanded range of vitamin D metabolites - to screen German and French cohorts of hypercalcemia patients, to identify patients with altered vitamin D metabolism where involvement of CYP24A1 or SLC34A1 mutation had been ruled out, and possessed normal 25-OH-D :24,25-(OH) D ratios. Read More

View Article and Full-Text PDF

The BBSome: a nexus controlling energy metabolism in the brain.

J Clin Invest 2021 Apr;131(8)

Institute of Innate Immunity, Department of Biophysical Imaging, Medical Faculty, University of Bonn, Bonn, Germany.

Bardet-Biedl syndrome (BBS) is a syndromic ciliopathy that has obesity as a cardinal feature. BBS is caused by mutations in BBS genes. BBS proteins control primary cilia function, and BBS mutations therefore lead to dysfunctional primary cilia. Read More

View Article and Full-Text PDF

Biallelic variants in LIG3 cause a novel mitochondrial neurogastrointestinal encephalomyopathy.

Brain 2021 Apr 15. Epub 2021 Apr 15.

Department of Morphology, Surgery and Experimental Medicine, St. Anna Hospital, University of Ferrara, Ferrara, 44124, Italy.

Abnormal gut motility is a feature of several mitochondrial encephalomyopathies, and mutations in genes such as TYMP and POLG, have been linked to these rare diseases. The human genome encodes three DNA ligases, of which only one, ligase III (LIG3), has a mitochondrial splice variant and is crucial for mitochondrial health. We investigated the effect of reduced LIG3 activity and resulting mitochondrial dysfunction in seven patients from three independent families, who showed the common occurrence of gut dysmotility and neurological manifestations reminiscent of mitochondrial neurogastrointestinal encephalomyopathy. Read More

View Article and Full-Text PDF

Association of common genetic variants of gene with the risk of type 2 diabetes mellitus.

Nucleosides Nucleotides Nucleic Acids 2021 Apr 14:1-11. Epub 2021 Apr 14.

Medical Genomics Research Center, Islamic Azad Tehran Medical Sciences University, Tehran, Iran.

Type 2 diabetes mellitus (T2DM) is a multifactorial polygenic disease. Potassium inwardly-rectifying channel, subfamily J, member 11 ( gene mutations can result in susceptibility of T2DM. The aim of this study is to investigate the relationship between risk of T2DM and its complications (retinopathy & renal) and polymorphisms rs5210 and rs5215 of the gene in a group of Iranian population. Read More

View Article and Full-Text PDF

Genetic Mapping of a new allele, in .

MicroPubl Biol 2021 Apr 8;2021. Epub 2021 Apr 8.

Biology Department, University of Detroit Mercy, Detroit, MI USA.

Genetic screens provide a mechanism to identify genes involved with different cellular and organismal processes. Using a Flp/FRT screen in the eye we identified mutations that result in alterations and de-regulation of cell growth and division. From this screen a group of undergraduate researchers part of the Fly-CURE consortium mapped and characterized a new allele of the gene , Read More

View Article and Full-Text PDF

Discovery of novel potential KIT inhibitors for the treatment of gastrointestinal stromal tumor.

Open Life Sci 2021 3;16(1):303-310. Epub 2021 Apr 3.

School of Life and Pharmaceutical Sciences, Dalian University of Technology, 2 Dagong Road, Liaodongwan New District, Panjin 124221, Liaoning, China.

Numerous inhibitors of tyrosine-protein kinase KIT, a receptor tyrosine kinase, have been explored as a viable therapy for the treatment of gastrointestinal stromal tumor (GIST). However, drug resistance due to acquired mutations in KIT makes these drugs almost useless. The present study was designed to screen the novel inhibitors against the activity of the KIT mutants through pharmacophore modeling and molecular docking. Read More

View Article and Full-Text PDF

Genetics of and male infertility.

Transl Androl Urol 2021 Mar;10(3):1391-1400

Division of Urology, Department of Surgery, Mount Sinai Hospital and Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.

Cystic fibrosis (CF) is a rare autosomal-recessive disorder manifested as multisystem organ dysfunction. The cystic fibrosis transmembrane conductance regulator (CFTR) protein functions as an ion transporter on the epithelium of exocrine glands, regulating secretion viscosity. The gene, encoded on chromosome 7, is required for the production and trafficking of the intact and functional CFTR protein. Read More

View Article and Full-Text PDF

SCAMP3 is a mutant EGFR phosphorylation target and a tumor suppressor in lung adenocarcinoma.

Oncogene 2021 Apr 13. Epub 2021 Apr 13.

Thoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD, USA.

Mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain constitutively activate EGFR resulting in lung tumorigenesis. Activated EGFR modulates downstream signaling by altering phosphorylation-driven interactions that promote growth and survival. Secretory carrier membrane proteins (SCAMPs) are a family of transmembrane proteins that regulate recycling of receptor proteins, including EGFR. Read More

View Article and Full-Text PDF

Panels and models for accurate prediction of tumor mutation burden in tumor samples.

NPJ Precis Oncol 2021 Apr 13;5(1):31. Epub 2021 Apr 13.

Bioinformatics Unit, Fundación Instituto Leloir, Buenos Aires, C1405BWE, Avda. Patricias Argentinas 435 C1405BWE, Ciudad Autonoma de Buenos Aires, Argentina.

Immune checkpoint blockade (ICB) is becoming standard-of-care in many types of human malignancies, but patient selection is still imperfect. Tumor mutation burden (TMB) is being evaluated as a biomarker for ICB in clinical trials, but most of the sequencing panels used to estimate it are inadequately designed. Here, we present a bioinformatics-based method to select panels and mathematical models for accurate TMB prediction. Read More

View Article and Full-Text PDF