Carbohydrate deficient glycoprotein syndrome type IV: deficiency of dolichyl-P-Man : Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferase

Type IV of the carbohydrate deficient glycoprotein syndromes (CDGS) is char acterized by microcephaly, severe epilepsy, minimal psychomotor development and partial deficiency of sialic acids in serum glycoproteins. Here we sho w that the molecular defect in the index patient is a missense mutation in the gene encoding the mannosyltransferase that transfers mannose from dolic hyl-phosphate mannose on to the lipid-linked oligosaccharide (LLO) intermed iate Man(5)GlcNAc(2)-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 t runcated oligosaccharides in addition to that of full-length oligosaccharid es and because of the incomplete utilization of N-glycosylation sites. The mannosyltransferase is the structural and functional orthologue of the Sacc haromyces cerevisiae ALG3 gene.