Cover Image

SEC24C deficiency causes trafficking and glycosylation abnormalities in an epileptic encephalopathy with cataracts and dyserythropoeisis

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 corres...

Full description

Saved in:
Bibliographic Details
Main Authors: Bögershausen, Nina (Author) , Cavdarli, Büsranur (Author) , Nagai, Taylor H. (Author) , Milev, Miroslav P. (Author) , Wolff, Alexander (Author) , Mehranfar, Mahsa (Author) , Schmidt, Julia (Author) , Choudhary, Dharmendra (Author) , Gutiérrez-Gutiérrez, Óscar (Author) , Cyganek, Lukas (Author) , Saint-Dic, Djenann (Author) , Zibat, Arne (Author) , Köhrer, Karl (Author) , Wollenweber, Tassilo E. (Author) , Wieczorek, Dagmar (Author) , Altmüller, Janine (Author) , Borodina, Tatiana (Author) , Kaçar, Dilek (Author) , Haliloğlu, Göknur (Author) , Li, Yun (Author) , Thiel, Christian (Author) , Sacher, Michael (Author) , Knapik, Ela W. (Author) , Yigit, Gökhan (Author) , Wollnik, Bernd (Author)
Format: Article (Journal)
Language:English
Published: May 8, 2025
In: The journal of clinical investigation
Year: 2025, Volume: 10, Pages: 1-21
ISSN:1558-8238
DOI:10.1172/jci.insight.173484
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1172/jci.insight.173484
Verlag, kostenfrei, Volltext: https://insight.jci.org/articles/view/173484
Get full text
Author Notes:Nina Bögershausen, Büsranur Cavdarli, Taylor H. Nagai, Miroslav P. Milev, Alexander Wolff, Mahsa Mehranfar, Julia Schmidt, Dharmendra Choudhary, Óscar Gutiérrez-Gutiérrez, Lukas Cyganek, Djenann Saint-Dic, Arne Zibat, Karl Köhrer, Tassilo E. Wollenweber, Dagmar Wieczorek, Janine Altmüller, Tatiana Borodina, Dilek Kaçar, Göknur Haliloğlu, Yun Li, Christian Thiel, Michael Sacher, Ela W. Knapik, Gökhan Yigit, and Bernd Wollnik
Description
Summary: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.
Item Description:Veröffentlicht: 25. März 2025
Gesehen am 24.09.2025
Physical Description:Online Resource
ISSN:1558-8238
DOI:10.1172/jci.insight.173484

Similar Items