{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T17:06:52Z","timestamp":1789837612953,"version":"4.0.1"},"reference-count":81,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6721","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Science"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:p>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 \u201cTRiCopathies.\u201d<\/jats:p>","DOI":"10.1126\/science.adp8721","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T13:59:00Z","timestamp":1730383140000},"page":"516-525","update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":30,"title":["Brain malformations and seizures by impaired chaperonin function of TRiC"],"prefix":"10.1126","volume":"386","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5324-9155","authenticated-orcid":true,"given":"Florian","family":"Kraft","sequence":"first","affiliation":[{"name":"Institute for Human Genetics and Genomic Medicine, Medical Faculty, RWTH Aachen University, Aachen, 52074, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3828-4235","authenticated-orcid":true,"given":"Piere","family":"Rodriguez-Aliaga","sequence":"additional","affiliation":[{"name":"Department of Biology, Stanford University, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1447-1982","authenticated-orcid":true,"given":"Weimin","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5148-8526","authenticated-orcid":true,"given":"Lena","family":"Franken","sequence":"additional","affiliation":[{"name":"Institute for Human Genetics and Genomic Medicine, Medical Faculty, RWTH Aachen University, Aachen, 52074, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6280-3464","authenticated-orcid":true,"given":"Kamil","family":"Zajt","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, RWTH Aachen University Hospital, Aachen 52074, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimah","family":"Hasan","sequence":"additional","affiliation":[{"name":"Department for Diagnostic and Interventional Neuroradiology, RWTH Aachen University Hospital, Aachen 52074, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1010-3292","authenticated-orcid":true,"given":"Ting-Ting","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biology, Stanford University, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6802-1356","authenticated-orcid":true,"given":"Elisabetta","family":"Flex","sequence":"additional","affiliation":[{"name":"Department of Oncology and Molecular Medicine, Istituto Superiore di Sanit\u00e0, Rome 00161, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Hentschel","sequence":"additional","affiliation":[{"name":"Leibniz- Institut f\u00fcr Analytische Wissenschaften -ISAS- e.V., Dortmund 44139, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9881-5467","authenticated-orcid":true,"given":"A. 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