Jos Jansen

1 Introduction to hepatic congenital glycosylation disorders 21 Chapter Research question Hypothesis Research model 2, 3 Research question 1: can we find the pathogenic gene(s) in eight families with abnormal glycosylation 1.Vph2p and Vma22p, two yeast proteins, have TMEM199 and CCDC115 as human orthologs 1.Comparative genomics 2. pathogenic variants in CCDC115 and TMEM199 are causative for the geno- and phenotype in the investi- gated families 2. WES, sanger sequencing, Western blot 3. CCDC115 and TMEM199 are located in the ERGIC Immunofluorescence studies 4 Research question 2: can we correlate the phenotype of CCDC115 and TMEM199 deficiency to more com- mon diseases Abnormal Golgi homeosta- sis due to CCDC115 and TMEM199 deficiency can be correlated to defective intracellular lipid trans- port via COP I and COP II vesicles Narrative review 5 Research question 3: can screening in a pre-selected liver patient group identify more patients with CDG? The a-priori chance of find- ing a CDG in patients with liver disease is higher Retrospective screening study 5 Research question 4: can we use our cohort to gain more insight in differenc- es between primary and secondary glycosylation defects Hyposialylation and hy- perfucosylation are more frequently seen in liver disease tIEF and QTOF mass spectrometry