Zentrum für Kinder- und Jugendmedizin der Universität Heidelberg
Congenital Disorders of Glycosylation (CDG)
comprise a group of autosomal recessive inherited human diseases, which affect the de novo biosynthesis of glycoproteins. The transfer of oligosaccharide chains onto newly synthesized proteins is one of the most widespread forms of co- and posttranslational modifications which is found in animals, plants and bacteria. Glycoproteins are located inside cells predominantly in subcellular organelles and in cellular membranes and most abundantly in extracellular fluids and matrices. The oligosaccharide moieties of glycoproteins affect their folding, their transport as well as their biological activity and stability. The complex process of protein glycosylation requires more than a hundred glycosyltransferases, glycosidases and transport proteins. Oligosaccharide moieties are connected to glycoproteins predominantly by either N-glykosidic linkages, in which glycans are linked to amino groups of asparagine side chains, or by O-glykosidic linkage, where the glycans are bound to hydroxyl groups of serine or threonine side chains. CDG present with multi organ involvement, which mostly includes neurological symptoms. CDG is subdivided into two groups. CDG-I comprise deficiencies which either affect the biosynthesis of dolichol-linked oligosaccharides or the transfer of oligosaccharides onto newly synthesized proteins by the oligosaccharyltransferase complex in the endoplasmic reticulum. CDG-II affect the subsequent trimming and elongation of N-glycans in the endoplasmic reticulum and the Golgi.
Besides the search for new molecular defects in glycoprotein biosynthesis, we are currently generating mouse models for several known CDG-types. These models will allow investigations on therapeutic approaches as well as studies on the general role of protein glycosylation which is in many points still poorly understood.
Im Neuenheimer Feld 153