| Title: |
Brain malformations and seizures by impaired chaperonin function of TRiC. |
| Authors: |
Kraft, Florian; Rodriguez-Aliaga, Piere; Yuan, Weimin; Franken, Lena; Zajt, Kamil; Hasan, Dimah; Lee, Ting-Ting; Flex, Elisabetta; Hentschel, Andreas; Innes, A Micheil; Zheng, Bixia; Julia Suh, Dong Sun; Knopp, Cordula; Lausberg, Eva; Krause, Jeremias; Zhang, Xiao-Meng; Trapane, Pamela; Carroll, Riley; McClatchey, Martin; Fry, Andrew A.E.; Wang, Lisa; Giesselmann, Sebastian; Hoang, Hieu; Baldridge, Dustin; Silverman, Gary A; Radio, Francesca Clementina; Bertini, Enrico; Ciolfi, Andrea; Blood, Katherine KA; de Sainte Agathe, Jean-Madeleine; Charles, Perrine; Bergant, Gaber; Čuturilo, Goran; Peterlin, Borut; Diderich, Karin; Streff, Haley; Robak, Laurie; Oegema, Renske; van Binsbergen, Ellen; Herriges, John; Saunders, Carol J; Maier, Andrea; Wolking, Stefan; Weber, Yvonne Y.G.; Lochmüller, Hanns; Meyer, Stefanie; Aleman, Alberto; Polavarapu, Kiran; Nicolas, Gaelle; Goldenberg, Alice; Guyant, Lucie; Pope, Kathleen; Hehmeyer, Katherine KN; Monaghan, Kristin KG; Quade, Annegret; Smol, Thomas; Caumes, Roseline; Duerinckx, Sarah; Depondt, Chantal; Van Paesschen, Wim; Rieubland, Claudine; Poloni, Claudia; Guipponi, Michel; Arcioni, Severine; Meuwissen, Marije E C; Jansen, Anna C M A.C.; Rosenblum, Jessica; Haack, Tobias Bernd; Bertrand, Miriam; Gerstner, Lea; Magg, Janine; Riess, Olaf; Schulz, Jörg B; Wagner, Norbert; Wiesmann, Martin; Weis, Joachim; Eggermann, Thomas; Begemann, Matthias; Roos, Andreas; Häusler, Martin; Schedl, Tim; Tartaglia, Marco; Bremer, Juliane; Pak, Stephen SC; Frydman, Judith; Elbracht, Miriam; Kurth, Ingo |
| Source: |
Science, 386 (6721 |
| Publisher Information: |
2024-11-01 |
| Document Type: |
Electronic Resource |
| Abstract: |
Malformations of the brain are common and vary in severity, from negligible to potentially fatal. Their causes have not been fully elucidated. Here, we report pathogenic variants in the core protein-folding machinery TRiC/CCT in individuals with brain malformations, intellectual disability, and seizures. The chaperonin TRiC is an obligate hetero-oligomer, and we identify variants in seven of its eight subunits, all of which impair function or assembly through different mechanisms. Transcriptome and proteome analyses of patient-derived fibroblasts demonstrate the various consequences of TRiC impairment. The results reveal an unexpected and potentially widespread role for protein folding in the development of the central nervous system and define a disease spectrum of "TRiCopathies."; SCOPUS: ar.j; info:eu-repo/semantics/published |
| Index Terms: |
Sciences bio-médicales et agricoles; Humans; Male; Brain -- abnormalities -- diagnostic imaging -- metabolism; Chaperonin Containing TCP-1 -- chemistry -- genetics -- metabolism; Fibroblasts -- metabolism; Intellectual Disability -- genetics -- metabolism; Protein Folding; Protein Subunits -- metabolism -- genetics; Proteome -- metabolism; Seizures -- diagnostic imaging -- genetics -- metabolism; Transcriptome; Magnetic Resonance Imaging; Caenorhabditis elegans; Adult; info:eu-repo/semantics/article; info:ulb-repo/semantics/articlePeerReview; info:ulb-repo/semantics/openurl/article |
| URL: |
https://dipot.ulb.ac.be/dspace/bitstream/2013/385304/3/science.adp8721.pdf; http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/385304; https://worldcat.org/search?q=on:EQY+http://difusion-oai.ulb.ac.be/oai/request+DCG_ENTIRE_REPOSITORY+CNTCOLL |
| Availability: |
Open access content. Open access content; 1 full-text file(s): info:eu-repo/semantics/openAccess |
| Note: |
1 full-text file(s): application/pdf; English |
| Other Numbers: |
EQY oai:dipot.ulb.ac.be:2013/385304; uri/info:doi/10.1126/science.adp8721; uri/info:pmid/39480921; uri/info:scp/85208290432; 1493368645 |
| Contributing Source: |
UNIVERSITE LIBRE DE BRUXELLES; From OAIster®, provided by the OCLC Cooperative. |
| Accession Number: |
edsoai.on1493368645 |
| Database: |
OAIster |