Glycosylation is a complex process in which sugars (glycans) are attached to proteins, mainly in the ER and Golgi. These glycans carry essential biological information and regulate processes such as brain development, immune function, and cell growth. Defects in glycosylation can lead to disorders including immune dysfunction, cancer, and liver disease, making glycans promising diagnostic markers. Congenital Disorders of Glycosylation (CDGs) are rare genetic diseases caused by mutations that disrupt this process. Due to highly variable symptoms, diagnosis often requires advanced molecular techniques. This thesis applied multiple molecular technologies to improve CDG diagnostics and understand disease mechanisms. A new glycoproteomics workflow was developed and validated for routine use, enabling detection of previously missed cases. Additionally, a targeted method identified a biomarker for MOGS-CDG, leading to new diagnoses. Omics analysis of NANS-CDG revealed unexpected pathway interactions and therapeutic opportunities. Overall, these approaches enhance diagnostics and deepen insight into CDG pathophysiology.
Merel Post (1993) earned a Bachelor in Biomedical Sciences and a Master in Molecular and Cellular Life Sciences at Utrecht University. She continued her studies and started a PhD at Radboudumc on omics-based diagnostics for congenital glycosylation disorders. Since 2023, she works as Study Director at Charles River Laboratories, focusing on preclinical drug metabolism, biomarker assays, and method development for complex biomolecules