Jos Jansen

Chapter 1 18 Figure 3 . A. a typical tIEF pattern. The most abundant band is the Transferrin isoform with four sialic acids. B . QTOF MS of transferrin as a tool to define new groups of glycosylation disorders. The x-axis represents the deconvoluted atomic mass unit (amu) and the y-axis the abundance. The mass of the intact glycoprotein is 79.555 amu. Outline of this thesis In this thesis, I set out to obtain more insight in the association between abnormal glycosylation and liver disease in CDG. The incentive were patients from eight families with similar hepatic symptoms and a similar abnormal QTOF MS profile. Despite strong clinical and biochemical clues that these families had a mutation in the same gene (or a gene in the same pathway), regular genetic workup failed. This workup included linkage analysis, targeted sequencing for known Golgi homeostasis defects and exome sequencing. The general aims of this thesis are to identify the pathogenic variants in these families, to identify more families, and to characterize the function of the newly found proteins. Another aim was to explore glycosylation in patients with severe liver transplantation. The following research questions were formulated: