AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders
| Title: | AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders |
|---|---|
| Authors: | Salpietro V; Dixon CL; Guo H; Bello OD; Vandrovcova J; Efthymiou S; Maroofian R; Heimer G; Burglen L; Valence S; Torti E; Hacke M; Rankin J; Tariq H; Colin E; Procaccio V; Striano P; Mankad K; Lieb A; Chen S; Pisani L; Bettencourt C; Männikkö R; Manole A; Brusco A; Grosso E; Ferrero GB; Armstrong-Moron J; Gueden S; Bar-Yosef O; Tzadok M; Monaghan KG; Santiago-Sim T; Person RE; Cho MT; Willaert R; Yoo Y; Chae JH; Quan Y; Wu H; Wang T; Bernier RA; Xia K; Blesson A; Jain M; Motazacker MM; Jaeger B; Schneider AL; Boysen K; Muir AM; Myers CT; Gavrilova RH; Gunderson L; Schultz-Rogers L; Klee EW; Dyment D; Osmond M; Parellada M; Llorente C; Gonzalez-Peñas J; Carracedo A; Van Haeringen A; Ruivenkamp C; Nava C; Heron D; Nardello R; Iacomino M; Minetti C; Skabar A; Fabretto A; SYNAPS Study Group; Raspall-Chaure M; Chez M; Tsai A; Fassi E; Shinawi M; Constantino JN; De Zorzi R; Fortuna S; Kok F; Keren B; Bonneau D; Choi M; Benzeev B; Zara F; Mefford HC; Scheffer IE; Clayton-Smith J; Macaya A; Rothman JE; Eichler EE; Kullmann DM; Houlden H; Hanna MG; Bugiardini E; Hostettler I; O'Callaghan B; Khan A; Cortese A; O'Connor E; Yau WY; Bourinaris T; Kaiyrzhanov R; Chelban V; Madej M; Diana MC; Vari MS; Pedemonte M; Bruno C; Balagura G; Scala M; Fiorillo C; Nobili L; Malintan NT; Zanetti MN; Krishnakumar SS; Lignani G; Jepson JEC; Broda P; Baldassari S; Rossi P; Fruscione F; Madia F; Traverso M; De-Marco P; Pérez-Dueñas B; Munell F; Kriouile Y; El-Khorassani M; Karashova B; Avdjieva D; Kathom H; Tincheva R; Van-Maldergem L; Nachbauer W; Boesch S; Gagliano A; Amadori E; Goraya JS; Sultan T; Kirmani S; Ibrahim S; Jan F; Mine J; Banu S; Veggiotti P; Zuccotti GV; Ferrari MD; Van Den Maagdenberg AMJ; Verrotti A; Marseglia GL; Savasta S; Soler MA; Scuderi C; Borgione E; Chimenz R; Gitto E; Dipasquale V; Sallemi A; Fusco M; Cuppari C; Cutrupi MC; Ruggieri M; Cama A; Capra V; Mencacci NE; Boles R; Gupta N; Kabra M; Papacostas S; Zamba-Papanicolaou E; Dardiotis E; Maqbool S; Rana N; Atawneh O; Lim SY; Shaikh F; Koutsis G; Breza M; Coviello DA; Dauvilliers YA; AlKhawaja I; AlKhawaja M; Al-Mutairi F; Stojkovic T; Ferrucci V; Zollo M; Alkuraya FS; Kinali M; Sherifa H; Benrhouma H; Turki IBY; Tazir M; Obeid M; Bakhtadze S; Saadi NW; Zaki MS; Triki CC; Benfenati F; Gustincich S; Kara M; Belcastro V; Specchio N; Capovilla G; Karimiani EG; Salih AM; Okubadejo NU; Ojo OO; Oshinaike OO; Oguntunde O; Wahab K; Bello AH; Abubakar S; Obiabo Y; Nwazor E; Ekenze O; Williams U; Iyagba A; Taiwo L; Komolafe M; Senkevich K; Shashkin C; Zharkynbekova N; Koneyev K; Manizha G; Isrofilov M; Guliyeva U; Salayev K; Khachatryan S; Rossi S; Silvestri G; Haridy N; Ramenghi LA; Xiromerisiou G; David E; Aguennouz M; Fidani L; Spanaki C; Tucci A. |
| Contributors: | Salpietro, V; Dixon, Cl; Guo, H; Bello, Od; Vandrovcova, J; Efthymiou, S; Maroofian, R; Heimer, G; Burglen, L; Valence, S; Torti, E; Hacke, M; Rankin, J; Tariq, H; Colin, E; Procaccio, V; Striano, P; Mankad, K; Lieb, A; Chen, S; Pisani, L; Bettencourt, C; Männikkö, R; Manole, A; Brusco, A; Grosso, E; Ferrero, Gb; Armstrong-Moron, J; Gueden, S; Bar-Yosef, O; Tzadok, M; Monaghan, Kg; Santiago-Sim, T; Person, Re; Cho, Mt; Willaert, R; Yoo, Y; Chae, Jh; Quan, Y; Wu, H; Wang, T; Bernier, Ra; Xia, K; Blesson, A; Jain, M; Motazacker, Mm; Jaeger, B; Schneider, Al; Boysen, K; Muir, Am; Myers, Ct; Gavrilova, Rh; Gunderson, L; Schultz-Rogers, L; Klee, Ew; Dyment, D; Osmond, M; Parellada, M; Llorente, C; Gonzalez-Peñas, J; Carracedo, A; Van Haeringen, A; Ruivenkamp, C; Nava, C; Heron, D; Nardello, R; Iacomino, M; Minetti, C; Skabar, A; Fabretto, A; SYNAPS Study, Group; Raspall-Chaure, M; Chez, M; Tsai, A; Fassi, E; Shinawi, M; Constantino, Jn; De Zorzi, R; Fortuna, S; Kok, F; Keren, B; Bonneau, D; Choi, M; Benzeev, B; Zara, F; Mefford, Hc; Scheffer, Ie; Clayton-Smith, J; Macaya, A; Rothman, Je; Eichler, Ee; Kullmann, Dm; Houlden, H; Hanna, Mg; Bugiardini, E; Hostettler, I; O'Callaghan, B; Khan, A; Cortese, A; O'Connor, E |
| Publisher Information: | Nature Publishing Group; Londra |
| Publication Year: | 2019 |
| Collection: | Università degli Studi di Genova: CINECA IRIS |
| Subject Terms: | Adolescent; Adult; Brain; Child; Preschool; Cohort Studie; Female; Heterozygote; Human; Infant; Intellectual Disability; Loss of Function Mutation; Magnetic Resonance Imaging; Male; Neurodevelopmental Disorder; Receptors; AMPA; Young Adult |
| Description: | 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. |
| Document Type: | article in journal/newspaper |
| File Description: | ELETTRONICO |
| Language: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/31300657; info:eu-repo/semantics/altIdentifier/wos/WOS:000475295700001; volume:10; firstpage:1; lastpage:16; numberofpages:16; journal:NATURE COMMUNICATIONS; https://hdl.handle.net/11567/973820 |
| DOI: | 10.1038/s41467-019-10910-w |
| Availability: | https://hdl.handle.net/11567/973820; https://doi.org/10.1038/s41467-019-10910-w |
| Rights: | info:eu-repo/semantics/openAccess |
| Accession Number: | edsbas.C34462A9 |
| Database: | BASE |