Congenital disorder of glycosylation type Ik (CDG-Ik): a defect of mannosyltransferase I.

Abstract

This study describes the discovery of a new inherited disorder of glycosylation named "CDG-Ik." CDG-Ik (congenital disorder of glycoslyation type Ik) is based on a defect of human mannosyltransferase I (MT-I [MIM 605907]), an enzyme necessary for the elongation of dolichol-linked chitobiose during N-glycan biosynthesis. Mutations in semiconserved regions in the corresponding gene, HMT-1 (yeast homologue, Alg1), in two patients caused drastically reduced enzyme activity, leading to a severe disease with death in early infancy. One patient had a homozygous point mutation (c.773C-->T, S258L), whereas the other patient was compound heterozygous for the mutations c.773C-->T and c.1025A-->C (E342P). Glycosylation and growth of Alg1-deficient PRY56 yeast cells, showing a temperature-sensitive phenotype, could be restored by the human wild-type allele, whereas only slight restoration was observed after transformation with the patients' alleles.

• Authors: Christian Kranz, Jonas Denecke, Ludwig Lehle, Kristina Sohlbach, Stefanie Jeske, Friedhelm Meinhardt, Rainer Rossi, Sonja Gudowius, Thorsten Marquardt
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 74 Issue 3 Pg. 545-51 (Mar 2004) ISSN: 0002-9297 [Print] United States
• PMID: 14973782 (Publication Type: Journal Article)

Chemical References

• Polyisoprenyl Phosphate Monosaccharides
• N-acetylglucosaminylpyrophosphoryldolichol
• Mannosyltransferases
• chitobiosyldiphosphodolichol beta-mannosyltransferase

Topics

• Genetic Diseases, Inborn
• Glycosylation
• Humans
• Mannosyltransferases (genetics, metabolism)
• Polyisoprenyl Phosphate Monosaccharides (metabolism)
• Saccharomyces (enzymology, genetics, metabolism)