| Title: |
De Novo Disruption of the Proteasome Regulatory Subunit PSMD12 Causes a Syndromic Neurodevelopmental Disorder |
| Authors: |
Küry, Sébastien; Besnard, Thomas; Ebstein, Frédéric; Khan, Tahir N.; Gambin, Tomasz; Douglas, Jessica; Bacino, Carlos A.; Craigen, William J; Sanders, Stephan J.; Lehmann, Andrea; Latypova, Xenia; Khan, Kamal; Pacault, Mathilde; Sacharow, Stephanie; Glaser, Kimberly; Bieth, Eric; Perrin-Sabourin, Laurence; Jacquemont, Marie-Line; Cho, Megan T.; Roeder, Elizabeth; Denommé-Pichon, Anne-Sophie; Monaghan, Kristin G.; Yuan, Bo; Xia, Fan; Simon, Sylvain; Bonneau, Dominique; Parent, Philippe; Gilbert-Dussardier, Brigitte; Odent, Sylvie; Toutain, Annick; Pasquier, Laurent; Barbouth, Deborah; Shaw, Chad A.; Patel, Ankita; Smith, Janice L.; Bi, Weimin; Schmitt, Sébastien; Deb, Wallid; Nizon, Mathilde; Mercier, Sandra; Vincent, Marie; Rooryck, Caroline; Malan, Valérie; Briceno, Ignacio; Gómez, Alberto; Nugent, Kimberly M.; Gibson, James B.; Cogné, Benjamin; Lupski, James R.; Stessman, Holly A. F.; Eichler, Evan E.; Retterer, Kyle; Yang, Yaping; Redon, Richard; Katsanis, Nicholas; Rosenfeld, Jill A.; Kloetzel, Peter-Michael; Golzio, Christelle; Bézieau, Stéphane; Stankiewicz, Paweł; Isidor, Bertrand |
| Contributors: |
Service de génétique médicale - Unité de génétique clinique Nantes; Université de Nantes (UN)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes); Charité - UniversitätsMedizin = Berlin University Medicine; Duke University Medical Center; Warsaw University of Technology Warsaw; Boston Children's Hospital; Baylor College of Medicine (BCM); Baylor University; University of California San Francisco (UC San Francisco); University of California (UC); University of Miami Coral Gables; Service Génétique Médicale CHU Toulouse; Institut Fédératif de Biologie (IFB); Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie CHU Toulouse; Centre Hospitalier Universitaire de Toulouse (CHU Toulouse); Hôpital Robert Debré; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Centre Hospitalier Universitaire de La Réunion (CHU La Réunion); GeneDx Gaithersburg, MD, USA; Centre Hospitalier Universitaire d'Angers (CHU Angers); LabEX IGO Immunothérapie Grand Ouest; Nantes Université (Nantes Univ); Anti-Tumor Immunosurveillance and Immunotherapy (CRCINA-ÉQUIPE 3); Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA); Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE); Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE); Université de Nantes (UN)-Université de Nantes (UN); Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes); Service de génétique Angers; Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers); Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI); Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Centre Hospitalier Régional Universitaire de Brest (CHRU Brest); Centre hospitalier universitaire de Poitiers = Poitiers University Hospital (CHU de Poitiers La Milétrie ); Institut de Génétique et Développement de Rennes (IGDR); 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); Service de génétique clinique Rennes; Université de Rennes (UR)-Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Pontchaillou -hôpital Sud; Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Pontchaillou; Service de génétique CHRU Tours; Centre Hospitalier Régional Universitaire de Tours (CHRU Tours); Imaging, Brain & Neuropsychiatry (iBraiN); Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM); Centre Hospitalier Universitaire de Bordeaux (CHU Bordeaux); Laboratoire Histologie Embryologie Cytogénétique CHU Necker; Hôpital Necker - Enfants Malades AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Pontificia Universidad Javeriana (PUJ); University of Washington Seattle; Howard Hughes Medical Institute Seattle; Howard Hughes Medical Institute (HHMI); ITX - unité de recherche de l'institut du thorax (ITX); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE); National Heart, Lung, and Blood Institute; Wellcome Trust; French Ministry of Health; HUGODIMS, 2013, RC14_0107, Health Regional Agency from Poitou-Charentes; U54HG006542, US National Human Genome Research Institute |
| Source: |
ISSN: 0002-9297. |
| Publisher Information: |
CCSD; Elsevier (Cell Press) |
| Publication Year: |
2017 |
| Collection: |
Université François-Rabelais de Tours: HAL |
| Subject Terms: |
PSMD12; ubiquitin; syndromic neurodevelopmental disorder; intellectual disability; proteasome 26S; RPN5; [SDV.GEN]Life Sciences [q-bio]/Genetics |
| Description: |
International audience ; Degradation of proteins by the ubiquitin-proteasome system (UPS) is an essential biological process in the development of eukaryotic organisms. Dysregulation of this mechanism leads to numerous human neurodegenerative or neurodevelopmental disorders. Through a multi-center collaboration, we identified six de novo genomic deletions and four de novo point mutations involving PSMD12, encoding the non-ATPase subunit PSMD12 (aka RPN5) of the 19S regulator of 26S proteasome complex, in unrelated individuals with intellectual disability, congenital malformations, ophthalmologic anomalies, feeding difficulties, deafness, and subtle dysmorphic facial features. We observed reduced PSMD12 levels and an accumulation of ubiquitinated proteins without any impairment of proteasome catalytic activity. Our PSMD12 loss-of-function zebrafish CRISPR/Cas9 model exhibited microcephaly, decreased convolution of the renal tubules, and abnormal craniofacial morphology. Our data support the biological importance of PSMD12 as a scaffolding subunit in proteasome function during development and neurogenesis in particular; they enable the definition of a neurodevelopmental disorder due to PSMD12 variants, expanding the phenotypic spectrum of UPS-dependent disorders. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/28132691; PUBMED: 28132691; PUBMEDCENTRAL: PMC5294671 |
| DOI: |
10.1016/j.ajhg.2017.01.003 |
| Availability: |
https://univ-rennes.hal.science/hal-01478814; https://univ-rennes.hal.science/hal-01478814v1/document; https://univ-rennes.hal.science/hal-01478814v1/file/main.pdf; https://doi.org/10.1016/j.ajhg.2017.01.003 |
| Rights: |
https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.B51958CA |
| Database: |
BASE |