Mutations in SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm
| Autor: | Severine Leclerc, Steven J.M. Jones, Harry C. Dietz, Silja Barbara Burkhard, Sandrine Faure, Philippe Chetaille, Gilles R.X. Hickson, Julie Castilloux, Gregor Andelfinger, Pascal de Santa Barbara, Jean-Marc Côté, Nour El Amine, Florian Wünnemann, Christoph Preuss, Natacha Gosset, Damian Labuda, Shing Hei Zhan, Maryse Thibeault, Jessica Piché, Jeroen Bakkers, D. Woodrow Benson, Michel Cameron, Claudia Moreau, Ines Boufaied, Christine Houde, Carmen Gagnon, Emmanuelle Lemyre, Elena Gallo-McFarlane, Anders Jonzon, Elizabeth Tuck, Antonella Galli, Yaoqing Shen, Michèle Jomphe |
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| Přispěvatelé: | CHU de Québec–Université Laval, Université Laval [Québec] (ULaval), Research Center, CHU Sainte-Justine, Universite de Montreal, Montreal, Quebec, Canada, Centre de recherche de l'hôpital Sainte Justine, CHU Sainte Justine [Montréal]-CHU Sainte Justine [Montréal], Université de Montréal (UdeM), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Howard Hughes Medical Institute (HHMI), CHU Sainte Justine [Montréal], cardiology, Department of Pediatrics, Ophthalmology and Pharmacology, Hôpital Sainte-Justine, Hubrecht Institute for Developmental Biology and Stem Cell Research |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Chromosomal Proteins
Non-Histone Cell Cycle Proteins Arrhythmias Muscle Smooth Vascular Enteric Nervous System 0302 clinical medicine Transforming Growth Factor beta Zebrafish Genetics 0303 health sciences Gene knockdown biology Cell Cycle Quebec Karyotype Syndrome Founder Effect 3. Good health Cell biology Chromosomal Proteins 030220 oncology & carcinogenesis Gene Knockdown Techniques Medical genetics Muscle Smooth biological phenomena cell phenomena and immunity Abnormalities Multiple Cardiac Muscle Contraction Signal Transduction Senescence medicine.medical_specialty Cohesin complex Article 03 medical and health sciences Vascular medicine Animals Humans Abnormalities Multiple Pathological 030304 developmental biology [SDV.GEN]Life Sciences [q-bio]/Genetics Arrhythmias Cardiac Non-Histone Fibroblasts biology.organism_classification Gastrointestinal Tract Intestinal Diseases Karyotyping Mutation Enteric nervous system |
| Zdroj: | Nature Genetics Nature Genetics, Nature Publishing Group, 2014, ⟨10.1038/ng.3113⟩ Nature Genetics, 46(11), 1245-9. Nature Publishing Group |
| ISSN: | 1061-4036 1546-1718 |
| DOI: | 10.1038/ng.3113⟩ |
| Popis: | International audience; The pacemaking activity of specialized tissues in the heart and gut results in lifelong rhythmic contractions. Here we describe a new syndrome characterized by Chronic Atrial and Intestinal Dysrhythmia, termed CAID syndrome, in 16 French Canadians and 1 Swede. We show that a single shared homozygous founder mutation in SGOL1, a component of the cohesin complex, causes CAID syndrome. Cultured dermal fibroblasts from affected individuals showed accelerated cell cycle progression, a higher rate of senescence and enhanced activation of TGF-b signaling. Karyotypes showed the typical railroad appearance of a centromeric cohesion defect. Tissues derived from affected individuals displayed pathological changes in both the enteric nervous system and smooth muscle. Morpholino-induced knockdown of sgol1 in zebrafish recapitulated the abnormalities seen in humans with CAID syndrome. Our findings identify CAID syndrome as a novel generalized dysrhythmia, suggesting a new role for SGOL1 and the cohesin complex in mediating the integrity of human cardiac and gut rhythm. |
| Databáze: | OpenAIRE |
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