![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
13MB |
![[thumbnail of Supplemental Material]](https://edoc.mdc-berlin.de/style/images/fileicons/other.png) |
Other (Supplemental Material)
2MB |
| Item Type: | Article |
|---|---|
| Title: | SEC24C deficiency causes trafficking and glycosylation abnormalities in an epileptic encephalopathy with cataracts and dyserythropoeisis |
| Creators Name: | Bögershausen, N., Cavdarli, B., Nagai, T., Milev, M.P., Wolff, A., Mehranfar, M., Schmidt, J., Choudhary, D., Gutiérrez-Gutiérrez, Ó., Cyganek, L., Saint-Dic, D., Zibat, A., Köhrer, K., Wollenweber, T.E., Wieczorek, D., Altmüller, J., Borodina, T., Kaçar, D., Haliloğlu, G., Li, Y., Thiel, C., Sacher, M., Knapik, E.W., Yigit, G. and Wollnik, B. |
| Abstract: | As a major component of intracellular trafficking, the coat protein complex II (COPII) is indispensable for cellular function during embryonic development and throughout life. The 4 SEC24 proteins (A–D) are essential COPII components involved in cargo selection and packaging. A human disorder corresponding to alterations of SEC24 function is currently known only for SEC24D. Here, we reported that biallelic loss of SEC24C leads to a syndrome characterized by primary microcephaly, brain anomalies, epilepsy, hearing loss, liver dysfunction, anemia, and cataracts in an extended consanguineous family with 4 affected individuals. We showed that knockout of sec24C in zebrafish recapitulated important aspects of the human phenotype. SEC24C-deficient fibroblasts displayed alterations in the expression of several COPII components as well as impaired anterograde trafficking to the Golgi, indicating a severe impact on COPII function. Transcriptome analysis revealed that SEC24C deficiency also affected the proteasome and autophagy pathways. Moreover, a shift in the N-glycosylation pattern and deregulation of the N-glycosylation pathway suggested a possible secondary alteration of protein glycosylation, linking the described disorder with the congenital disorders of glycosylation. |
| Keywords: | Cataract, Epilepsy, Glycosylation, Golgi Apparatus, Microcephaly, Pedigree, Protein Transport, Vesicular Transport Proteins, Animals, Zebrafish |
| Source: | JCI Insight |
| ISSN: | 2379-3708 |
| Publisher: | American Society for Clinical Investigation |
| Volume: | 10 |
| Number: | 9 |
| Page Range: | e173484 |
| Date: | 8 May 2025 |
| Official Publication: | https://doi.org/10.1172/jci.insight.173484 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
