PUBLICATION
Brain malformations and seizures by impaired chaperonin function of TRiC
- Authors
- Kraft, F., Rodriguez-Aliaga, P., Yuan, W., Franken, L., Zajt, K., Hasan, D., Lee, T.T., Flex, E., Hentschel, A., Innes, A.M., Zheng, B., Julia Suh, D.S., Knopp, C., Lausberg, E., Krause, J., Zhang, X., Trapane, P., Carroll, R., McClatchey, M., Fry, A.E., Wang, L., Giesselmann, S., Hoang, H., Baldridge, D., Silverman, G.A., Radio, F.C., Bertini, E., Ciolfi, A., Blood, K.A., de Sainte Agathe, J.M., Charles, P., Bergant, G., Čuturilo, G., Peterlin, B., Diderich, K., Streff, H., Robak, L., Oegema, R., van Binsbergen, E., Herriges, J., Saunders, C.J., Maier, A., Wolking, S., Weber, Y., Lochmüller, H., Meyer, S., Aleman, A., Polavarapu, K., Nicolas, G., Goldenberg, A., Guyant, L., Pope, K., Hehmeyer, K.N., Monaghan, K.G., Quade, A., Smol, T., Caumes, R., Duerinckx, S., Depondt, C., Van Paesschen, W., Rieubland, C., Poloni, C., Guipponi, M., Arcioni, S., Meuwissen, M., Jansen, A.C., Rosenblum, J., Haack, T.B., Bertrand, M., Gerstner, L., Magg, J., Riess, O., Schulz, J.B., Wagner, N., Wiesmann, M., Weis, J., Eggermann, T., Begemann, M., Roos, A., Häusler, M., Schedl, T., Tartaglia, M., Bremer, J., Pak, S.C., Frydman, J., Elbracht, M., Kurth, I.
- ID
- ZDB-PUB-260409-18
- Date
- 2024
- Source
- Science (New York, N.Y.) 386: 516525516-525 (Journal)
- Registered Authors
- Bremer, Juliane, Zheng, Bixia
- Keywords
- none
- MeSH Terms
- none
- PubMed
- 39480921 Full text @ Science
Citation
Kraft, F., Rodriguez-Aliaga, P., Yuan, W., Franken, L., Zajt, K., Hasan, D., Lee, T.T., Flex, E., Hentschel, A., Innes, A.M., Zheng, B., Julia Suh, D.S., Knopp, C., Lausberg, E., Krause, J., Zhang, X., Trapane, P., Carroll, R., McClatchey, M., Fry, A.E., Wang, L., Giesselmann, S., Hoang, H., Baldridge, D., Silverman, G.A., Radio, F.C., Bertini, E., Ciolfi, A., Blood, K.A., de Sainte Agathe, J.M., Charles, P., Bergant, G., Čuturilo, G., Peterlin, B., Diderich, K., Streff, H., Robak, L., Oegema, R., van Binsbergen, E., Herriges, J., Saunders, C.J., Maier, A., Wolking, S., Weber, Y., Lochmüller, H., Meyer, S., Aleman, A., Polavarapu, K., Nicolas, G., Goldenberg, A., Guyant, L., Pope, K., Hehmeyer, K.N., Monaghan, K.G., Quade, A., Smol, T., Caumes, R., Duerinckx, S., Depondt, C., Van Paesschen, W., Rieubland, C., Poloni, C., Guipponi, M., Arcioni, S., Meuwissen, M., Jansen, A.C., Rosenblum, J., Haack, T.B., Bertrand, M., Gerstner, L., Magg, J., Riess, O., Schulz, J.B., Wagner, N., Wiesmann, M., Weis, J., Eggermann, T., Begemann, M., Roos, A., Häusler, M., Schedl, T., Tartaglia, M., Bremer, J., Pak, S.C., Frydman, J., Elbracht, M., Kurth, I. (2024) Brain malformations and seizures by impaired chaperonin function of TRiC. Science (New York, N.Y.). 386:516525516-525.
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."
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping