Article
- The EMBO Journal (1999) 18, 6816 - 6822
- doi:10.1093/emboj/18.23.6816
Carbohydrate deficient glycoprotein syndrome type IV: deficiency of dolichyl-P-Man:Man5 GlcNAc2-PP-dolichyl mannosyltransferase
Christian Körner1,5, Roland Knauer2,5, Ulrich Stephani3, Thorsten Marquardt4, Ludwig Lehle2 and Kurt von Figura1
- Georg-August-Universität Göttingen, Abteilung Biochemie II, Heinrich-Düker-Weg 12, D-37073 Göttingen, Germany
- Universität Regensburg, Lehrstuhl für Zellbiologie und Pflanzenphysiologie, Universitätsstrasse 31, D-93053 Regensburg, Germany
- Christian-Albrechts Universität zu Kiel, Klinik für Neuropaediatrie, Kiel Germany
- Klinik und Poliklinik für Kinderheilkunde, D-48149 Münster, Germany
- C.Körner and R.Knauer contributed equally to this work
Correspondence to:
Christian Körner, E-mail: koerner@ukb2-00.uni-bc.gwdg.de
Received 10 September 1999; Accepted 4 October 1999; Revised 4 October 1999
Abstract
Type IV of the carbohydrate deficient glycoprotein syndromes (CDGS) is characterized by microcephaly, severe epilepsy, minimal psychomotor development and partial deficiency of sialic acids in serum glycoproteins. Here we show that the molecular defect in the index patient is a missense mutation in the gene encoding the mannosyltransferase that transfers mannose from dolichyl-phosphate mannose on to the lipid-linked oligosaccharide (LLO) intermediate Man5GlcNAc2-PP-dolichol. The defect results in the accumulation of the LLO intermediate and, due to its leaky nature, a residual formation of full-length LLOs. N-glycosylation is abnormal because of the transfer of truncated oligosaccharides in addition to that of full-length oligosaccharides and because of the incomplete utilization of N-glycosylation sites. The mannosyltransferase is the structural and functional orthologue of the Saccharomyces cerevisiae ALG3 gene.
Keywords:
- ALG3 gene,
- carbohydrate deficient glycoprotein syndrome,
- dolichyl-P-Man:Man5GlcNAc2-PP-dolichyl mannosyltransferase
