Epistasis between RET and BBS mutations modulates enteric innervation and causes syndromic Hirschsprung disease
| Autor: | Hélène Dollfus, Andrew S. McCallion, Philip L. Beales, Nicholas Katsanis, Heather C. Etchevers, Anna Pelet, David M. McGaughey, Tania Attié-Bitach, Arnold Munnich, Jeanne Amiel, Clarisse Baumann, Jose L. Badano, Stanislas Lyonnet, Cecilia Gascue, Norann A. Zaghloul, Sophie Thomas, Candice Babarit, Loïc de Pontual, Seneca L. Bessling, Erica E. Davis |
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| Přispěvatelé: | Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University ( JHU ), Service de génétique médicale, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Unité fonctionnelle de génétique clinique, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), Institut Pasteur de Montevideo, Réseau International des Instituts Pasteur ( RIIP ) -Institut Pasteur de Montevideo, Molecular Medicine Unit, University College of London [London] ( UCL ) -Institute of Child Health, Department of Molecular and Comparative Pathology, Johns Hopkins University School of Medicine, Center for Human Disease Modeling, Duke university [Durham], Department of Molecular Biology and Genetics and Wilmer Eye Institute, Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Johns Hopkins University (JHU), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Réseau International des Instituts Pasteur (RIIP), University College of London [London] (UCL)-Institute of Child Health, Duke University [Durham], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Male
Cytoplasm MESH : Genotype MESH: Stomach MESH: Genotype MESH: Hirschsprung Disease MESH : Proteins 0302 clinical medicine Genotype MESH: Epistasis Genetic Missense mutation MESH : Enhancer Elements Genetic MESH: Proteins MESH : Female MESH : Proto-Oncogene Proteins c-ret [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics Zebrafish Genetics MESH : Epistasis Genetic 0303 health sciences Multidisciplinary biology Stomach Biological Sciences Pedigree 3. Good health Enhancer Elements Genetic Proto-Oncogene Proteins c-ret Female MESH : Mutation Microtubule-Associated Proteins congenital hereditary and neonatal diseases and abnormalities MESH : Cytoplasm MESH: Mutation MESH: Pedigree MESH : Male MESH : Stomach MESH : Family Health MESH: Proto-Oncogene Proteins c-ret 03 medical and health sciences Bardet–Biedl syndrome medicine Humans Hirschsprung Disease Allele MESH : Hirschsprung Disease Alleles 030304 developmental biology Family Health Neurocristopathy MESH: Humans MESH: Alleles MESH: Cytoplasm MESH : Humans Proteins Epistasis Genetic biology.organism_classification medicine.disease MESH: Male [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics MESH : Pedigree Mutation MESH: Family Health Cancer research Epistasis MESH: Enhancer Elements Genetic MESH : Alleles MESH: Female 030217 neurology & neurosurgery |
| 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, National Academy of Sciences, 2009, 106 (33), pp.13921-6. 〈10.1073/pnas.0901219106〉 Proceedings of the National Academy of Sciences; Vol 106 Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2009, 106 (33), pp.13921-6. ⟨10.1073/pnas.0901219106⟩ |
| ISSN: | 0027-8424 1091-6490 |
| DOI: | 10.1073/pnas.0901219106〉 |
| Popis: | Hirschsprung disease (HSCR) is a common, multigenic neurocristopathy characterized by incomplete innervation along a variable length of the gut. The pivotal gene in isolated HSCR cases, either sporadic or familial, is RET . HSCR also presents in various syndromes, including Shah–Waardenburg syndrome (WS), Down (DS), and Bardet–Biedl (BBS). Here, we report 3 families with BBS and HSCR with concomitant mutations in BBS genes and regulatory RET elements, whose functionality is tested in physiologically relevant assays. Our data suggest that BBS mutations can potentiate HSCR predisposing RET alleles, which by themselves are insufficient to cause disease. We also demonstrate that these genes interact genetically in vivo to modulate gut innervation, and that this interaction likely occurs through complementary, yet independent, pathways that converge on the same biological process. |
| Databáze: | OpenAIRE |
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