A canine Arylsulfatase G (ARSG) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis
| Autor: | Françoise Gray, Natasha J. Olby, Sandra Brahimi, Jean-Laurent Thibaud, Fanny Pilot-Storck, Marie Abitbol, Benoit Hedan, Catherine Caillaud, Jean-Philippe Puech, Marie Maurer, Stéphane Dréano, Christophe Hitte, Delphine Delattre, Françoise Delisle, Laurent Tiret, Stéphane Blot, Catherine André, Geneviève Aubin-Houzelstein, Jean-Jacques Panthier, Florence Bernex |
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| Přispěvatelé: | Génétique Moléculaire et Cellulaire (UGMC), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Laboratoire de neurobiologie, École nationale vétérinaire - Alfort (ENVA), Department of Clinical Sciences, North Carolina State University [Raleigh] (NC State), University of North Carolina System (UNC)-University of North Carolina System (UNC), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biochimie et génétique moléculaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Antagene, Service d'anatomie et cytologie pathologiques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Centre de radiothérapie-Scanner, De Villemeur, Hervé, École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), École nationale vétérinaire d'Alfort (ENVA), Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, MICEN-Vet, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Ecole Natl Vet Alfort, Fonctions et dysfonctions épithéliales - UFC (EA 4267) (FDE), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Alcatel-Thales III-V Lab (III-V Lab), THALES, Génétique fonctionnelle et médicale (GFM - ENVA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Génétique Moléculaire et Cellulaire ( UGMC ), Institut National de la Recherche Agronomique ( INRA ) -Ecole Nationale Vétérinaire d'Alfort, Ecole Nationale Vétérinaire d'Alfort, North Carolina State University [Raleigh] ( NCSU ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 ( UPD7 ), CERTO, sans affiliation, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), THALES [France] |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Male
Candidate gene [SDV]Life Sciences [q-bio] [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology [SDV.GEN] Life Sciences [q-bio]/Genetics 0403 veterinary science Gene Frequency Catalytic Domain Missense mutation Dog Diseases ComputingMilieux_MISCELLANEOUS Arylsulfatases Genetics 0303 health sciences Multidisciplinary Reverse Transcriptase Polymerase Chain Reaction Sulfatase Age Factors Chromosome Mapping 04 agricultural and veterinary sciences Biological Sciences 3. Good health Pedigree Cerebellar cortex dog lysosome Female [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Genotype 040301 veterinary sciences Molecular Sequence Data Mutation Missense Locus (genetics) Biology Polymorphism Single Nucleotide Cell Line 03 medical and health sciences Cerebellar Cortex Dogs Microscopy Electron Transmission Neuronal Ceroid-Lipofuscinoses medicine Animals Humans [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] 030304 developmental biology [SDV.GEN]Life Sciences [q-bio]/Genetics Genetic heterogeneity Gene Expression Profiling animal model Haplotype ataxia medicine.disease Molecular biology Chromosomes Mammalian Haplotypes [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] neurodegenerative Neuronal ceroid lipofuscinosis ATP-Binding Cassette Transporters [ SDV.GEN ] Life Sciences [q-bio]/Genetics [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, 2010, 107 (33), pp.14775-80. ⟨10.1073/pnas.0914206107⟩ Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2010, 107 (33), pp.14775-80. ⟨10.1073/pnas.0914206107⟩ Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2010, 107 (33), pp.14775-14780. ⟨10.1073/pnas.0914206107⟩ Proceedings of the National Academy of Sciences; Vol 107 Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2010, 107 (33), pp.14775-80. 〈10.1073/pnas.0914206107〉 Proceedings of the National Academy of Sciences Proceedings of the National Academy of Sciences of the United States of America, 2010, 107 (33), pp.14775-14780. ⟨10.1073/pnas.0914206107⟩ |
| ISSN: | 0027-8424 1091-6490 |
| DOI: | 10.1073/pnas.0914206107⟩ |
| Popis: | Neuronal ceroid lipofuscinoses (NCLs) represent the most common group of inherited progressive encephalopathies in children. They are characterized by progressive loss of vision, mental and motor deterioration, epileptic seizures, and premature death. Rare adult forms of NCL with late onset are known as Kufs’ disease. Loci underlying these adult forms remain unknown due to the small number of patients and genetic heterogeneity. Here we confirm that a late-onset form of NCL recessively segregates in US and French pedigrees of American Staffordshire Terrier (AST) dogs. Through combined association, linkage, and haplotype analyses, we mapped the disease locus to a single region of canine chromosome 9. We eventually identified a worldwide breed-specific variant in exon 2 of the Arylsulfatase G ( ARSG ) gene, which causes a p.R99H substitution in the vicinity of the catalytic domain of the enzyme. In transfected cells or leukocytes from affected dogs, the missense change leads to a 75% decrease in sulfatase activity, providing a functional confirmation that the variant might be the NCL-causing mutation. Our results uncover a protein involved in neuronal homeostasis, identify a family of candidate genes to be screened in patients with Kufs' disease, and suggest that a deficiency in sulfatase is part of the NCL pathogenesis. |
| Databáze: | OpenAIRE |
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