224 results match your criteria mutation truncates

Netrin-1 receptor UNC5C cleavage by active δ-secretase enhances neurodegeneration, promoting Alzheimer's disease pathologies.

Sci Adv 2021 Apr 16;7(16). Epub 2021 Apr 16.

Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.

Netrin-1, a family member of laminin-related secreted proteins, mediates axon guidance and cell migration during neural development. T835M mutation in netrin receptor UNC5C predisposes to the late-onset Alzheimer's disease (AD) and increases neuronal cell death. However, it remains unclear how this receptor is molecularly regulated in AD. Read More

View Article and Full-Text PDF

A Novel Truncating Mutation in HOMER2 Causes Nonsyndromic Progressive DFNA68 Hearing Loss in a Spanish Family.

Genes (Basel) 2021 Mar 12;12(3). Epub 2021 Mar 12.

Servicio de Genética, Hospital Universitario Ramón y Cajal, IRYCIS, Carretera de Colmenar km 9.100, 28034 Madrid, Spain.

Nonsyndromic hereditary hearing loss is a common sensory defect in humans that is clinically and genetically highly heterogeneous. So far, 122 genes have been associated with this disorder and 50 of them have been linked to autosomal dominant (DFNA) forms like DFNA68, a rare subtype of hearing impairment caused by disruption of a stereociliary scaffolding protein (HOMER2) that is essential for normal hearing in humans and mice. In this study, we report a novel HOMER2 variant (c. Read More

View Article and Full-Text PDF

SARS-CoV-2 variants combining spike mutations and the absence of ORF8 may be more transmissible and require close monitoring.

Filipe Pereira

Biochem Biophys Res Commun 2021 04 25;550:8-14. Epub 2021 Feb 25.

Centre for Functional Ecology, Department of Life Sciences, University of Coimbra, Calçada Martim de Freitas, 3000-456, Coimbra, Portugal; IDENTIFICA Genetic Testing, Rua Simão Bolívar 259 3° Dir Tras, 4470-214, Maia, Portugal. Electronic address:

The SARS-CoV-2 Variant of Concern 202012/01 (VOC-202012/01) emerged in southeast England and rapidly spread worldwide. This variant is believed to be more transmissible, with all attention being given to its spike mutations. However, VOC-202012/01 has also a mutation (Q27stop) that truncates the ORF8, a likely immune evasion protein. Read More

View Article and Full-Text PDF

Anastral Spindle 3/Rotatin Stabilizes Sol narae and Promotes Cell Survival in .

Mol Cells 2021 Jan;44(1):13-25

Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea.

Apoptosis and compensatory proliferation, two intertwined cellular processes essential for both development and adult homeostasis, are often initiated by the mis-regulation of centrosomal proteins, damaged DNA, and defects in mitosis. Fly Anastral spindle 3 (Ana3) is a member of the pericentriolar matrix proteins and known as a key component of centriolar cohesion and basal body formation. We report here that is a suppressor of lethality induced by the overexpression of Sol narae (Sona), a metalloprotease in a disintegrin and metalloprotease with thrombospondin motif (ADAMTS) family. Read More

View Article and Full-Text PDF
January 2021

The rax homeobox gene is mutated in the eyeless axolotl, Ambystoma mexicanum.

Dev Dyn 2020 Aug 30. Epub 2020 Aug 30.

Department of Cell Biology and Human Anatomy, University of California Davis School of Medicine, Davis, California, USA.

Background: Vertebrate eye formation requires coordinated inductive interactions between different embryonic tissue layers, first described in amphibians. A network of transcription factors and signaling molecules controls these steps, with mutations causing severe ocular, neuronal, and craniofacial defects. In eyeless mutant axolotls, eye morphogenesis arrests at the optic vesicle stage, before lens induction, and development of ventral forebrain structures is disrupted. Read More

View Article and Full-Text PDF

Discovery and Genomic Characterization of a 382-Nucleotide Deletion in ORF7b and ORF8 during the Early Evolution of SARS-CoV-2.

mBio 2020 07 21;11(4). Epub 2020 Jul 21.

Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore

To date, limited genetic changes in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome have been described. Here, we report a 382-nucleotide (nt) deletion in SARS-CoV-2 that truncates open reading frame 7b (ORF7b) and ORF8, removing the ORF8 transcription regulatory sequence (TRS) and eliminating ORF8 transcription. The earliest 382-nt deletion variant was detected in Singapore on 29 January 2020, with the deletion viruses circulating in the country and accounting for 23. Read More

View Article and Full-Text PDF

A 63-bp insertion in exon 2 of the porcine KIF21A gene is associated with arthrogryposis multiplex congenita.

Anim Genet 2020 Oct 20;51(5):820-823. Epub 2020 Jul 20.

Animal Genomics, Institute of Agricultural Science, D-USYS, ETH Zürich, Zürich, 8092, Switzerland.

A recessive form of arthrogryposis multiplex congenita (AMC) was detected 20 years ago in the Swiss Large White (SLW) pig population. A diagnostic marker test enabled the identification of carrier animals, but the underlying causal mutation remains unknown. To identify the mutation underlying AMC, we collected SNP chip genotyping data for 11 affected piglets and 23 healthy pigs. Read More

View Article and Full-Text PDF
October 2020

A frameshift variant in specificity protein 1 triggers superactivation of Sp1-mediated transcription in familial bone marrow failure.

Proc Natl Acad Sci U S A 2020 07 7;117(29):17151-17155. Epub 2020 Jul 7.

Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, E1 2AT London, United Kingdom.

Inherited bone marrow failure (BMF) syndromes are a heterogeneous group of diseases characterized by defective hematopoiesis and often predisposing to myelodysplastic syndrome (MDS) and acute myelogenous leukemia. We have studied a large family consisting of several affected individuals with hematologic abnormalities, including one family member who died of acute leukemia. By whole-exome sequencing, we identified a novel frameshift variant in the ubiquitously expressed transcription factor specificity protein 1 (). Read More

View Article and Full-Text PDF

A Frameshift Variant in a Rottweiler Dog with Footpad Hyperkeratosis.

Genes (Basel) 2020 04 24;11(4). Epub 2020 Apr 24.

School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

A single male Rottweiler dog with severe footpad hyperkeratosis starting at an age of eight weeks was investigated. The hyperkeratosis was initially restricted to the footpads. The footpad lesions caused severe discomfort to the dog and had to be trimmed under anesthesia every 8-10 weeks. Read More

View Article and Full-Text PDF

PRPS polymerization influences lens fiber organization in zebrafish.

Dev Dyn 2020 08 14;249(8):1018-1031. Epub 2020 Apr 14.

Howard Hughes Medical Institute (HHMI) Summer Institute, Marine Biological Laboratory, Woods Hole, Massachusetts, USA.

Background: The self-assembly of metabolic enzymes into filaments or foci highlights an intriguing mechanism for the regulation of metabolic activity. Recently, we identified the conserved polymerization of phosphoribosyl pyrophosphate synthetase (PRPS), which catalyzes the first step in purine nucleotide synthesis, in yeast and cultured mammalian cells. While previous work has revealed that loss of PRPS activity regulates retinal development in zebrafish, the extent to which PRPS filament formation affects tissue development remains unknown. Read More

View Article and Full-Text PDF

A Novel Frameshift Mutation in Abnormal Spindle-Like Microcephaly (ASPM) Gene in an Iranian Patient with Primary Microcephaly: A Case Report.

Iran J Public Health 2019 Nov;48(11):2074-2078

Department of Medical Genetics, Fardis Central Lab, Alborz, Iran.

Autosomal recessive primary microcephaly (MCPH) is a rare genetic disorder, leading to the defect of neurogenic brain development. Individuals with MCPH reveal reduced head circumference and intellectual disability. Several MCPH loci have been identified from several populations. Read More

View Article and Full-Text PDF
November 2019

Identification of a novel protein truncating mutation p.Asp98* in XPC associated with xeroderma pigmentosum in a consanguineous Pakistani family.

Mol Genet Genomic Med 2020 02 10;8(2):e1060. Epub 2020 Jan 10.

Diagnostic & Research Institute of Human Genetics, Medical University of Graz, Graz, Austria.

Background: Xeroderma pigmentosum (XP) is a rare genetic disorder, which is characterized by hyper-sensitivity to solar ultraviolet (UV) radiation. Clinical consequences of sun exposure are skin lesions and an increased risk of developing skin cancer. Genetic studies have identified eight genes associated with xeroderma pigmentosum. Read More

View Article and Full-Text PDF
February 2020

Apple ALMT9 Requires a Conserved C-Terminal Domain for Malate Transport Underlying Fruit Acidity.

Plant Physiol 2020 02 26;182(2):992-1006. Epub 2019 Nov 26.

Horticulture Section, School of Integrative Plant Science, Cornell University, Ithaca, New York 14853

Malate accumulation in the vacuole largely determines apple () fruit acidity, and low fruit acidity is strongly associated with truncation of , an ortholog of () in Arabidopsis (). A mutation at base 1,455 in the open reading frame of leads to a premature stop codon that truncates the protein by 84 amino acids at its C-terminal end. Here, we report that both the full-length protein, Ma1, and its naturally occurring truncated protein, ma1, localize to the tonoplast; when expressed in oocytes and cells, Ma1 mediates a malate-dependent inward-rectifying current, whereas the ma1-mediated transmembrane current is much weaker, indicating that ma1 has significantly lower malate transport activity than Ma1. Read More

View Article and Full-Text PDF
February 2020

Whole Exome Sequencing of an X-linked Thrombocytopenia Patient with Normal Sized Platelets.

Avicenna J Med Biotechnol 2019 Jul-Sep;11(3):253-258

Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.

Wiskott-Aldrich Syndrome () is a rare X-linked recessive Primary Immunodeficiency (PID) caused by mutations in gene which encodes a protein known as WASp. WASp plays important roles in cytoskeletal functions that compromise multiple aspects of normal cellular activity including proliferation, phagocytosis, immune synapse formation, adhesion and directed migration. WASp defect particularly causes platelets abnormality which is presented in forms of decrease of Mean Platelet Volume (MPV) and thrombocytopenia in most conditions; nevertheless, some studies reported patients with a normal or large size of platelets in recent years. Read More

View Article and Full-Text PDF

Frameshift Variant in Three Dogs with Recurrent Inflammatory Pulmonary Disease.

Genes (Basel) 2019 07 26;10(8). Epub 2019 Jul 26.

Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland.

We investigated three related Rough Collies with recurrent inflammatory pulmonary disease. The clinical symptoms were similar to primary ciliary dyskinesia (PCD). However, the affected dogs did not carry any known pathogenic PCD variants. Read More

View Article and Full-Text PDF

A glycine transporter SLC6A5 frameshift mutation causes startle disease in Spanish greyhounds.

Hum Genet 2019 May 7;138(5):509-513. Epub 2019 Mar 7.

Department of Genetics and Biochemistry, Clemson University, Clemson, SC, 29634, USA.

Startle disease, or hyperekplexia, is a glycinergic disorder characterized by hypertonia and apnea that is triggered by noise and/or touch. Mutations in five genes have been associated with startle disease in humans, dogs, cattle, and mice. We identified a novel recessive startle disease in a family of Spanish greyhounds. Read More

View Article and Full-Text PDF

A genetic variant of CYP2R1 identified in a cat with type 1B vitamin D-dependent rickets: a case report.

BMC Vet Res 2019 Feb 18;15(1):62. Epub 2019 Feb 18.

Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Medicine, School of Veterinary Medicine, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino, Tokyo, 180-8602, Japan.

Background: Vitamin D-dependent rickets is rare in animals and humans. Several types of this condition are associated with genetic variants related to vitamin D metabolism. This is the first report of type 1B vitamin D-dependent rickets in a cat. Read More

View Article and Full-Text PDF
February 2019

Clinical, Genetics, and Bioinformatic Characterization of Mutations Affecting an Essential Region of in Patients with BMND18.

Int J Endocrinol 2018 14;2018:8953217. Epub 2018 Oct 14.

School of Biology & Basic Medical Sciences, Medical College of Soochow University, Soochow University, Suzhou, Jiangsu, China.

Background: Bone mineral density quantitative trait locus 18 (BMND18, OMIM #300910) is a type of early-onset osteogenesis imperfecta (OI) caused by loss-of-function mutations in the PLS3 gene, which encodes plastin-3, a key protein in the formation of actin bundles throughout the cytoskeleton. Here, we report a patient with PLS3 mutation caused BMND18 and evaluated all the reported disease-causing mutations by bioinformatic analysis.

Methods: Targeted gene sequencing was performed to find the disease-causing mutation in our patient. Read More

View Article and Full-Text PDF
October 2018

GBGT1 is allelically diverse but dispensable in humans and naturally occurring anti-FORS1 shows an ABO-restricted pattern.

Transfusion 2018 08;58(8):2036-2045

Clinical Immunology and Transfusion Medicine, Division of Laboratory Medicine, Office of Medical Services.

Background: The FORS histo-blood group system was described in 2013 and much remains to be investigated regarding its genetic and immunohematologic characteristics, as well as its clinical importance. While presence of the c.887G>A-mutated GBGT1 gene, which results in FORS1 glycosphingolipid expression on human red blood cells (RBCs), is rare in the populations tested so far, naturally occurring anti-FORS1 in plasma appears common. Read More

View Article and Full-Text PDF

A frameshift variant in the EDA gene in Dachshunds with X-linked hypohidrotic ectodermal dysplasia.

Anim Genet 2018 Dec 2;49(6):651-654. Epub 2018 Oct 2.

Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001, Bern, Switzerland.

X-linked hypohidrotic ectodermal dysplasia (XLHED) is a genetic disease characterized by hypoplasia or absence of hair, teeth and sweat glands. The EDA gene, located on the X chromosome, encodes the type II transmembrane protein ectodysplasin A. Variants in the EDA gene can lead to XLHED in humans, mice, cattle and dogs. Read More

View Article and Full-Text PDF
December 2018

A mouse model of Angelman syndrome imprinting defects.

Hum Mol Genet 2019 01;28(2):220-229

Department of Molecular Genetics and Microbiology College of Medicine University of Florida, Gainsvile, FL, USA.

Angelman syndrome, Prader-Will syndrome and Dup15q syndrome map to a cluster of imprinted genes located at 15q11-q13. Imprinting at this domain is regulated by an imprinting control region consisting of two distinct elements, the Angelman syndrome imprinting center (AS-IC) and the Prader-Willi syndrome imprinting center (PWS-IC). Individuals inheriting deletions of the AS-IC exhibit reduced expression of the maternally expressed UBE3A gene and biallelic expression of paternal-only genes. Read More

View Article and Full-Text PDF
January 2019

A Novel Loss-of-Function Variant in Transmembrane Protein 263 (TMEM263) of Autosomal Dwarfism in Chicken.

Front Genet 2018 7;9:193. Epub 2018 Jun 7.

Animal Breeding and Genomics, Wageningen University & Research, Wageningen, Netherlands.

Autosomal dwarfism (adw) in chickens is a growth deficiency caused by a recessive mutation. Characteristic for adw is an approximately 30% growth reduction with short shank. The adw variant was first recognized in the Cornell K-strain of White Leghorns, but the genetic causal variant remained unknown. Read More

View Article and Full-Text PDF

Fulminant hepatitis B virus (HBV) infection in an infant following mother-to-child transmission of an e-minus HBV mutant: Time to relook at HBV prophylaxis in South African infants.

S Afr Med J 2018 04 25;108(5):389-392. Epub 2018 Apr 25.

Paediatric Infectious Diseases Unit, Red Cross War Memorial Children's Hospital, Cape Town, South Africa; and Department of Paediatrics and Child Health, Faculty of Health Sciences, University of Cape Town, South Africa.

The prevalence of hepatitis B virus (HBV) infection in pregnant women is high in South Africa (SA), yet prophylaxis to prevent mother-to-child transmission (MTCT) falls short of international recommendations. We describe a 10-week-old infant who developed fulminant hepatic failure following MTCT. The mother was hepatitis e-antibody positive and had a viral load of only 760 IU/mL. Read More

View Article and Full-Text PDF

Biosynthesis of Tropolones in Streptomyces spp.: Interweaving Biosynthesis and Degradation of Phenylacetic Acid and Hydroxylations on the Tropone Ring.

Appl Environ Microbiol 2018 06 31;84(12). Epub 2018 May 31.

State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, People's Republic of China

Tropolonoids are important natural products that contain a unique seven-membered aromatic tropolone core and exhibit remarkable biological activities. 3,7-Dihydroxytropolone (DHT) isolated from species is a multiply hydroxylated tropolone exhibiting antimicrobial, anticancer, and antiviral activities. In this study, we determined the DHT biosynthetic pathway by heterologous expression, gene deletion, and biotransformation. Read More

View Article and Full-Text PDF

Congenital myasthenic syndromes in Turkey: Clinical clues and prognosis with long term follow-up.

Neuromuscul Disord 2018 04 28;28(4):315-322. Epub 2017 Nov 28.

Department of Neurology, Mayo Clinic, Rochester, MN, USA.

Congenital myasthenic syndromes (CMS) are a group of hereditary disorders affecting the neuromuscular junction. Here, we present clinical, electrophysiological and genetic findings of 69 patients from 51 unrelated kinships from Turkey. Genetic tests of 60 patients were performed at Mayo Clinic. Read More

View Article and Full-Text PDF

Targeted deletion of the zebrafish actin-bundling protein L-plastin (lcp1).

PLoS One 2018 2;13(1):e0190353. Epub 2018 Jan 2.

Department of Biological Sciences, DePaul University, Chicago, Illinois, United States of America.

Regulation of the cytoskeleton is essential for cell migration in health and disease. Lymphocyte cytosolic protein 1 (lcp1, also called L-plastin) is a hematopoietic-specific actin-bundling protein that is highly conserved in zebrafish, mice and humans. In addition, L-plastin expression is documented as both a genetic marker and a cellular mechanism contributing to the invasiveness of tumors and transformed cell lines. Read More

View Article and Full-Text PDF
February 2018

A 12.3-kb Duplication Within the Gene in Pigs Affected by Von Willebrand Disease Type 3.

G3 (Bethesda) 2018 02 2;8(2):577-585. Epub 2018 Feb 2.

Department of Fundamental Research, Werlhof Institute GmbH, 30159 Hannover, Germany.

Von Willebrand Disease (VWD) type 3 is a serious and sometimes fatal hereditary bleeding disorder. In pigs, the disease has been known for decades, and affected animals are used as models for the human disease. Due to the recessive mode of inheritance of VWD type 3, severe bleeding is typically seen in homozygous individuals. Read More

View Article and Full-Text PDF
February 2018

Breakpoint mapping and haplotype analysis of translocation t(1;12)(q43;q21.1) in two apparently independent families with vascular phenotypes.

Mol Genet Genomic Med 2018 01 23;6(1):56-68. Epub 2017 Nov 23.

Department of Health, National Institute for Health and Welfare, Helsinki, Finland.

Background: The risk of serious congenital anomaly for de novo balanced translocations is estimated to be at least 6%. We identified two apparently independent families with a balanced t(1;12)(q43;q21.1) as an outcome of a "Systematic Survey of Balanced Chromosomal Rearrangements in Finns. Read More

View Article and Full-Text PDF
January 2018

Congenital Myasthenic Syndrome due to mutations in a family from Chile.

Eur J Transl Myol 2017 06 20;27(3):6832. Epub 2017 Sep 20.

Department of Neurology, University of California Davis, Davis CA, USA

Congenital myasthenic syndromes (CMS) are neuromuscular transmission disorders caused by mutations in genes encoding neuromuscular junction proteins. A 61-year-old female and her older sister showed bilateral ptosis, facial and proximal limb weakness, and scoliosis since childhood. Another female sibling had milder signs, while other family members were asymptomatic. Read More

View Article and Full-Text PDF

A disulfide bond A-like oxidoreductase is a strong candidate gene for self-incompatibility in apricot (Prunus armeniaca) pollen.

J Exp Bot 2017 Nov;68(18):5069-5078

Instituto de Biología Molecular y Celular de Plantas (IBMCP), Universidad Politécnica de Valencia-Consejo Superior de Investigaciones Científicas. C/Ingeniero Fausto Elio s/n, 46022 Valencia, Spain.

S-RNase based gametophytic self-incompatibility (SI) is a widespread prezygotic reproductive barrier in flowering plants. In the Solanaceae, Plantaginaceae and Rosaceae gametophytic SI is controlled by the pistil-specific S-RNases and the pollen S-locus F-box proteins but non-S-specific factors, namely modifiers, are also required. In apricot, Prunus armeniaca (Rosaceae), we previously mapped two pollen-part mutations that confer self-compatibility in cultivars Canino and Katy at the distal end of chromosome 3 (M-locus) unlinked to the S-locus. Read More

View Article and Full-Text PDF
November 2017