Science (New York, N.Y.) · 2024

Brain malformations and seizures by impaired chaperonin function of TRiC.

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди

Обработка статьи · этапы, ошибки и управление

Загрузка состояния…

История · было → стало

Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.

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 Xiaomeng, Trapane Pamela, Carroll Riley, McClatchey Martin, Fry Andrew E, Wang Lisa, Giesselmann Sebastian, Hoang Hieu, Baldridge Dustin, Silverman Gary A, Radio Francesca Clementina, Bertini Enrico, Ciolfi Andrea, Blood Katherine A, 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, Lochmüller Hanns, Meyer Stefanie, Aleman Alberto, Polavarapu Kiran, Nicolas Gael, Goldenberg Alice, Guyant Lucie, Pope Kathleen, Hehmeyer Katherine N, Monaghan Kristin G, Quade Annegret, Smol Thomas, Caumes Roseline, Duerinckx Sarah, Depondt Chantal, Van Paesschen Wim, Rieubland Claudine, Poloni Claudia, Guipponi Michel, Arcioni Severine, Meuwissen Marije, Jansen Anna C, Rosenblum Jessica, Haack Tobias B, 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 C, Frydman Judith, Elbracht Miriam, Kurth Ingo

Аннотация

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."

Предметные рубрики MeSH

Humans Male Brain Chaperonin Containing TCP-1 Fibroblasts Intellectual Disability Protein Folding Protein Subunits Proteome Seizures Transcriptome Magnetic Resonance Imaging Caenorhabditis elegans Adult

Brain malformations and seizures by impaired chaperonin function of TRiC.

Ошибки и ограничения

Аннотация

Предметные рубрики MeSH