EC Number   |
General Information |
Reference |
|---|
   2.4.1.265 | malfunction |
ALG8 deficiency (CDG Ih), leads to protein N-glycosylation defects caused by malfunction of Dol-P-Glc:Glc1-Man9-GlcNAc2-P-P-Dol glucosyltransferase resulting in inefficient addition of the second glucose residue onto lipid-linked oligosaccharides. The lipid-linked oligosaccharide profile of the patient shows the accumulation of incomplete precursor structures corresponding to GlcNAc2Man9 and GlcNAc2-Man9Glc1. Two ALG8 mutations in heterozygous form are detected in the patient. The first mutation (c.139A>C), is combined with a c.1090C>T mutation. The index mutation, which is translated into the missense mutation p.T47P, is inherited from the father. The c.1090C>T mutation resulting in a premature stop codon (p.R364X) is found in heterozygous form in the mother, whereas it is not found in 150 healthy controls. The prognosis of patients with ALG8 deficiency is unfavourable. The majority of affected children have early onset of the disease with heterogeneous symptoms including multiple organ dysfunction, coagulopathy and protein-losing enteropathy |
709391 |
| 2.4.1.265 | malfunction |
CDG type Ih is caused by a deficiency of the dolichyl-P-Glc:Glc1Man9GlcNAc2-PP-dolichyl alpha1,3-glucosyltransferase. The defect leads to an accumulation of Dol-PP-Glc-NAc2Man9 and Dol-PP-GlcNAc2Man9Glc1 in the endoplasmic reticulum of patients fibroblasts that can be detected by analyzing the lipid-linked oligosaccharyl intermediates. Two mildly affected siblings with CDG-Ih caused by two novel mutations are described. While one mutation (c.1434delC) causes a frame shift resulting in a premature termination codon (p.485X), the point mutation of the other allele (c.845C>T, p.A282V) causes an amino acid replacement in a highly conserved region of the hALG8 gene. The two siblings show similar symptoms, including pseudo-gynecomastia, epicanthus, muscular hypotonia, mental retardation and ataxia, expanding the genetic and clinical spectrum of CDG-Ih |
709971 |
| 2.4.1.265 | malfunction |
cells carrying the alg8-1 mutation accumulate Glc1Man9GlcNAc2-lipid both in vivo and in vitro |
708964 |
| 2.4.1.265 | malfunction |
congenital disorder of glycosylation type Ih (CDG-Ih) is caused by a defect in the dolichyl-P-Glc:Glc1 Man9GlcNAc2-PP-dolichyl alpha1,3-glucosyltransferase (ALG8). Accumulation of the lipid-linked oligosaccharyl intermediates Dol-PP-GlcNAc2Man9 and Dol-PP-GlcNAc2Man9Glc1 in patients' fibroblasts. Mutation analysis of the ALG8 gene identifies in both families a compound heterozygosity for a splice site mutation and a missense mutation (family 1: c.96-2A>G and p.T47P; family 2: c.672+4A>G and p.G275D). The functional effect of the ALG8 splice mutations is analysed on mRNA and the effect of the missense mutations is assayed in ALG8 deficient yeast strains. The molecular and clinical features of three patients from two families with an ALG8 deficiency are described. All three patients show severe, life-threatening multi organ failure and die within their first months of life |
709484 |
| 2.4.1.265 | malfunction |
patient with inefficient addition of the second glucose residue onto lipid-linked oligosaccharide. The patient possesses only 1020% normal amounts of mRNA encoding the enzyme, dolichyl-P-glucose:Glc1Man9GlcNAc2-PP-dolichyl alpha3-glucosyltransferase (hALG8p), which catalyzes this reaction. Sequencing of hALG8 genomic DNA reveals exon 4 to contain a base deletion in one allele and a base insertion in the other. Both mutations give rise to premature stop codons predicted to generate severely truncated proteins. Because the translation inhibitor emetine is shown to stabilize the hALG8 mRNA from the patient to normal levels, it is likely that both transcripts undergo nonsensemediated mRNA decay. As the cells from the patient are successfully complemented with wild type hALG8 cDNA, it is concluded that these mutations are the underlying cause of this new CDG I subtype that we propose be called CDG Ih |
708978 |
| 2.4.1.265 | malfunction |
the ALG8 protein is a hydrophobic protein that is not essential for the vegetative growth of yeast. The lack of this protein results in underglycosylation of secreted proteins |
710441 |
| 2.4.1.265 | physiological function |
deletion of algK, a protein essential for alginate secretion, in an alginate-overproducing strain, PDO300, interferes with the polymerization of alginate, suggesting that in the absence of AlgK, the polymerase and copolymerase subunits, Alg8 and Alg44, are destabilized. Deletion of Alg8 resulted in the absence of AlgK, AlgX, and Alg44 from the envelope fraction and leads to a complete loss of production of alginate |
735487 |
| 2.4.1.265 | physiological function |
generation of a marker-free isogenic double-gene-knockout mutant lacking Alg8 and 44. This mutant lost the mucoid phenotype and production of alginate. A direct interaction exists between the membrane-anchored glycosyltransferase Alg8 and the copolymerase Alg44 proteins |
-, 736726 |
