6533b7cffe1ef96bd12580b5
RESEARCH PRODUCT
AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders.
Vincenzo Salpietro12 3140Christine L. Dixon4140Hui Guo56 140Oscar D. Bello Stephanie Efthymiou 14Reza Maroofian1Gali Heimer7Lydie Burglen 8Stephanie Valence 9Erin Torti 10Moritz Hacke11Julia Rankin12Huma Tariq1Estelle Colin1314Vincent Procaccio1314Pasquale Striano23Kshitij Mankad15Andreas Lieb 4Sharon Chen16Laura Pisani16Conceicao Bettencourt 17Roope Männikkö 1Andreea Manole1Alfredo Brusco 18Enrico Grosso18Giovanni Battista Ferrero19Judith Armstrong-moron20Sophie Gueden21Omer Bar-yosef7Michal Tzadok7Kristin G. Monaghan10Teresa Santiago-sim10Richard E. Person10Megan T. Cho10Rebecca Willaert10Yongjin Yoo22Jong-hee Chae23Yingting Quan6Huidan Wu6Tianyun Wang56Raphael A. Bernier24Kun Xia6Alyssa Blesson25Mahim Jain25Mohammad M. Motazacker26Bregje Jaeger27Amy L. Schneider 28Katja Boysen28Alison M. Muir 29Candace T. Myers30Ralitza H. Gavrilova31Lauren Gunderson31Laura Schultz-rogers 31Eric W. Klee31David Dyment32Matthew Osmond3233 34Mara Parellada35Cloe Llorente36Javier Gonzalez-peñas37Angel Carracedo3839Arie Van Haeringen40Claudia Ruivenkamp40Caroline Nava41Delphine Heron41Rosaria Nardello42Michele Iacomino43Carlo Minetti23Aldo Skabar44Antonella Fabretto44Synaps Study Groupmiquel Raspall-chaure45Michael Chez46Anne Tsai47Emily Fassi48Marwan Shinawi48John N. Constantino49Rita De Zorzi50Sara Fortuna 50Fernando Kok5152Boris Keren41Dominique Bonneau1314Murim Choi 22Bruria Benzeev7Federico Zara43Heather C. Mefford29Ingrid E. Scheffer28Jill Clayton-smith5354Alfons Macaya45James E. Rothman455Evan E. Eichler 556Dimitri M. Kullmann 4 &Amp;Henry Houlden 1Synaps Study Group Michael G. Hanna1Enrico Bugiardini1Isabel Hostettler1Benjamin O’callaghan1Alaa Khan1Andrea Cortese1Emer O’connor1Wai Y. Yau1Thomas Bourinaris1Rauan Kaiyrzhanov1Viorica Chelban1Monika Madej1Maria C. Diana2Maria S. Vari2Marina Pedemonte2Claudio Bruno2Ganna Balagura3Marcello Scala3Chiara Fiorillo3Lino Nobili3Nancy T. Malintan4Maria N. Zanetti4Shyam S. Krishnakumar4Gabriele Lignani4James E. C. Jepson4Paolo Broda43Simona Baldassari43Pia Rossi43Floriana Fruscione43Francesca Madia43Monica Traverso43Patrizia De-marco43Belen Pérez-dueñas45Francina Munell45Yamna Kriouile57Mohamed El-khorassani57Blagovesta Karashova58Daniela Avdjieva58Hadil Kathom58Radka Tincheva58Lionel Van-maldergem59Wolfgang Nachbauer60Sylvia Boesch60Antonella Gagliano61Elisabetta Amadori62Jatinder S. Goraya63Tipu Sultan64Salman Kirmani65Shahnaz Ibrahim66Farida Jan66Jun Mine67Selina Banu68Pierangelo Veggiotti69Gian V. Zuccotti69Michel D. Ferrari70Arn M. J. Van Den Maagdenberg70Alberto Verrotti71Gian L. Marseglia72Salvatore Savasta72Miguel A. Soler73Carmela Scuderi74Eugenia Borgione74Roberto Chimenz75Eloisa Gitto75Valeria Dipasquale75Alessia Sallemi75Monica Fusco75Caterina Cuppari75Maria C. Cutrupi75Martino Ruggieri76Armando Cama77Valeria Capra77Niccolò E. Mencacci78Richard Boles79Neerja Gupta80Madhulika Kabra80Savvas Papacostas81Eleni Zamba-papanicolaou81Efthymios Dardiotis82Shazia Maqbool83Nuzhat Rana84Osama Atawneh85Shen Y. Lim86Farooq Shaikh87George Koutsis88Marianthi Breza88Domenico A. Coviello89Yves A. Dauvilliers90Issam Alkhawaja91Mariam Alkhawaja92Fuad Al-mutairi93Tanya Stojkovic94Veronica FerrucciMassimo ZolloFowzan S. Alkuraya96Maria Kinali97Hamed Sherifa98Hanene Benrhouma99Ilhem B. Y. Turki99Meriem Tazir100Makram Obeid101Sophia Bakhtadze102Nebal W. Saadi103Maha S. Zaki104Chahnez C. Triki105Fabio Benfenati106Stefano Gustincich106Majdi Kara107Vincenzo Belcastro108Nicola Specchio109Giuseppe Capovilla110Ehsan G. Karimiani111Ahmed M. Salih112Njideka U. Okubadejo113Oluwadamilola O. Ojo113Olajumoke O. Oshinaike113Olapeju Oguntunde113Kolawole Wahab114Abiodun H. Bello114Sanni Abubakar115Yahaya Obiabo116Ernest Nwazor117Oluchi Ekenze118Uduak Williams119Alagoma Iyagba120Lolade Taiwo121Morenikeji Komolafe122Konstantin Senkevich123Chingiz Shashkin124Nazira Zharkynbekova125Kairgali Koneyev126Ganieva Manizha127Maksud Isrofilov127Ulviyya Guliyeva128Kamran Salayev129Samson Khachatryan130Salvatore Rossi131Gabriella Silvestri131Nourelhoda Haridy132Luca A. Ramenghi133Georgia Xiromerisiou134Emanuele David135Mhammed Aguennouz136Liana Fidani137Cleanthe Spanaki138 &Amp;Arianna Tucci139subject
Male[SDV.GEN] Life Sciences [q-bio]/GeneticsIon channels in the nervous systemCohort Studiesfluids and secretionsLoss of Function MutationReceptorsAMPAAMPA receptorlcsh:ScienceChildreproductive and urinary physiologyAMPA receptor GluA2 neurodevelopmental disorders autism spectrum disorder glutamatergic synaptic transmission GRIA2neurodevelopmental disordersDevelopmental disordersQNeurodevelopmental disordersBrainMagnetic Resonance ImagingSettore MED/26 - NEUROLOGIAGluA2Child PreschoolFemaleAdultHeterozygoteAdolescentScienceautism spectrum disorderArticleYoung Adult[SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/PediatricsMESH: Intellectual Disability/genetics; Neurodevelopmental Disorders/genetics; Receptors AMPA/genetics; HeterozygoteIntellectual Disabilitymental disordersAdolescent; Adult; Brain; Child; Child Preschool; Cohort Studies; Female; Heterozygote; Humans; Infant; Intellectual Disability; Loss of Function Mutation; Magnetic Resonance Imaging; Male; Neurodevelopmental Disorders; Receptors AMPA; Young AdultHumansReceptors AMPAGRIA2PreschoolIon channel in the nervous system Developmental disorders Synaptic development NG sequencing[SDV.GEN]Life Sciences [q-bio]/Genetics[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatricsglutamatergic synaptic transmission[SCCO.NEUR]Cognitive science/Neuroscience[SCCO.NEUR] Cognitive science/NeuroscienceInfantNG sequencingSynaptic developmentIon channel in the nervous systemNext-generation sequencinglcsh:Qdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2019-07-12 |