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Article Dans Une Revue Nature Communications Année : 2019

AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders

Vincenzo Salpietro (1, 2, 3) , Christine Dixon (1) , Hui Guo (4) , Oscar Bello (5) , Jana J Vandrovcova (6) , Stephanie Efthymiou (7) , Reza Maroofian (8) , Gali Heimer (9) , Lydie Burglen (10) , Stephanie Valence (10) , Erin Torti (11) , Moritz Hacke (12) , Julia Rankin (13) , Huma Tariq (1) , Estelle Colin (14, 15) , Vincent Procaccio (14, 15) , Pasquale Striano (3) , Kshitij Mankad (16) , Andreas Lieb (1) , Sharon Chen (17) , Laura Pisani (18) , Conceição Bettencourt (1) , Roope Männikkö (1) , Andreea Manole (1) , Alfredo Brusco (19) , Enrico Del Grosso (19) , Giovanni Battista Ferrero (19) , Judith Armstrong-Moron (20) , Sophie Gueden (15) , Omer Bar-Yosef (21) , Michal Tzadok (21) , Kristin Monaghan (11) , Teresa Santiago-Sim (11) , Richard E. Person (11) , Megan T Cho (11) , Rebecca Willaert (11) , Yongjin Yoo (22) , Jong-Hee Chae (22) , Yingting Quan (23) , Huidan Wu (23) , Tianyun Wang (23) , Raphael Bernier (4) , Kun Xia (23) , Alyssa Blesson (24) , Mahim Jain (24) , Mohammad Motazacker (25) , Bregje Jaeger (25) , Amy Schneider (26) , Katja Boysen (26) , Alison Muir (4) , Candace Myers (4) , Ralitza Gavrilova (27) , Lauren Gunderson (27) , Laura Schultz-Rogers (27) , Eric Klee (28) , David Dyment (29) , Matthew M Osmond (30) , Mara Parellada (31) , Cloe Llorente (31) , Javier Gonzalez-Peñas (31) , Angel Carracedo (32) , Arie van Haeringen (33) , Claudia Ruivenkamp (33) , Caroline Nava (34) , Delphine Héron (35) , Rosaria Nardello (36) , Michele Iacomino (3) , Carlo Minetti (3) , Aldo Skabar (37) , Antonella Fabretto (37) , Miquel Raspall-Chaure (38) , Michael Chez (39) , Anne Tsai (40) , Emily Fassi (41) , Marwan Shinawi (42) , John N. Constantino (43) , Rita de Zorzi (44) , Sara Fortuna (37) , Fernando Kok (45) , Boris Keren (35) , Dominique Bonneau (46) , Murim Choi (47) , Bruria Benzeev (21) , Federico Zara (48) , Heather Mefford (4) , Ingrid E. Scheffer (26) , Jill Clayton-Smith (49) , Alfons Macaya (38) , James E Rothman (50) , Evan Eichler (4) , Dimitri Kullmann (1) , Henry Houlden (1) , Yves Dauvilliers (51)
1 UCL - University College of London [London]
2 Instituto Giannina Gaslini, Genoa
3 UniGe - Università degli studi di Genova = University of Genoa
4 University of Washington [Seattle]
5 Institute of Neurology, Queen Square, London
6 King‘s College London
7 UCL Institute of Neurology, Queen Square [London]
8 Genetics Research Centre - Molecular and Clinical Sciences Institute - St George’s [London, UK]
9 TAU - Tel Aviv University
10 CHU Trousseau [APHP]
11 GeneDx [Gaithersburg, MD, USA]
12 Heidelberg University Hospital [Heidelberg]
13 Royal Devon and Exeter NHS Foundation Trust [UK]
14 BNMI - Biologie Neurovasculaire et Mitochondriale Intégrée
15 CHU Angers - Centre Hospitalier Universitaire d'Angers
16 GOSH - Great Ormond Street Hospital for Children [London]
17 The University of Sydney
18 Hofstra University [Hempstead]
19 UNITO - Università degli studi di Torino = University of Turin
20 Hospital Sant Joan de Déu [Barcelona]
21 Safra Children's Hospital
22 Seoul National University Hospital
23 Central South University [Changsha]
24 Kennedy Krieger Institute [Baltimore]
25 UvA - University of Amsterdam [Amsterdam] = Universiteit van Amsterdam
26 University of Melbourne
27 Mayo Clinic [Rochester]
28 HSR - Department of Health Sciences Research [Mayo Clinic]
29 University of Ottawa [Ottawa]
30 UBC - University of British Columbia
31 UCM - Universidad Complutense de Madrid = Complutense University of Madrid [Madrid]
32 USC - Universidade de Santiago de Compostela [Spain]
33 Universiteit Leiden = Leiden University
34 ICM - Institut du Cerveau = Paris Brain Institute
35 CHU Pitié-Salpêtrière [AP-HP]
36 Università degli studi di Palermo - University of Palermo
37 Università degli studi di Trieste = University of Trieste
38 UAB - Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona
39 Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento
40 Children’s Hospital Colorado
41 WUSTL - Washington University in Saint Louis
42 Department of Molecular and Human Genetics
43 Department of Psychiatry
44 Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford
45 USP - Universidade de São Paulo = University of São Paulo
46 Service de Pédiatrie, CHUR Poitiers
47 SNU - Seoul National University [Seoul]
48 Pediatric Neurology and Neuromuscular Diseases Unit
49 University of Manchester [Manchester]
50 YSM - Yale School of Medicine [New Haven, Connecticut]
51 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
Gali Heimer
  • Fonction : Auteur
Lydie Burglen
  • Fonction : Auteur
  • PersonId : 922031
Boris Keren
Henry Houlden

Résumé

AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission.

Dates et versions

hal-02577355 , version 1 (14-05-2020)

Identifiants

Citer

Vincenzo Salpietro, Christine Dixon, Hui Guo, Oscar Bello, Jana J Vandrovcova, et al.. AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders. Nature Communications, 2019, 10 (1), ⟨10.1038/s41467-019-10910-w⟩. ⟨hal-02577355⟩
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