Deficiency of UDP-galactose:N-acetylglucosamine β-1,4-galactosyltransferase I causes the congenital disorder of glycosylation type IId
Bengt Hanßke, … , Kurt von Figura, Christian Körner
Bengt Hanßke, … , Kurt von Figura, Christian Körner
Published March 15, 2002
Citation Information: J Clin Invest. 2002;109(6):725-733. https://doi.org/10.1172/JCI14010.
View: Text | PDF
Article Genetics

Deficiency of UDP-galactose:N-acetylglucosamine β-1,4-galactosyltransferase I causes the congenital disorder of glycosylation type IId

Abstract

Deficiency of the Golgi enzyme UDP-Gal:N-acetylglucosamine β-1,4-galactosyltransferase I (β4GalT I) (E.C.2.4.1.38) causes a new congenital disorder of glycosylation (CDG), designated type IId (CDG-IId), a severe neurologic disease characterized by a hydrocephalus, myopathy, and blood-clotting defects. Analysis of oligosaccharides from serum transferrin by HPLC, mass spectrometry, and lectin binding revealed the loss of sialic acid and galactose residues. In skin fibroblasts and leukocytes, galactosyltransferase activity was reduced to 5% that of controls. In fibroblasts, a truncated polypeptide was detected that was about 12 kDa smaller in size than wild-type β4GalT I and that failed to localize to the Golgi apparatus. Sequencing of the β4GalT I cDNA and gene revealed an insertion of a single nucleotide (1031-1032insC) leading to premature translation stop and loss of the C-terminal 50 amino acids of the enzyme. The patient was homozygous and his parents heterozygous for this mutation. Expression of a corresponding mutant cDNA in COS-7 cells led to the synthesis of a truncated, inactive polypeptide, which localized to the endoplasmic reticulum.

Authors

Bengt Hanßke, Christian Thiel, Torben Lübke, Martin Hasilik, Stefan Höning, Verena Peters, Peter H. Heidemann, Georg F. Hoffmann, Eric G. Berger, Kurt von Figura, Christian Körner

×

Figure 4

Options: View larger image (or click on image) Download as PowerPoint
Identification of a 1031-1032insC mutation leading to premature translat...
Identification of a 1031-1032insC mutation leading to premature translation stop and loss of the C-terminal 50 amino acids of the patient’s β4GalT I. Sequence alignment of the PCR-amplified genomic DNA fragment from a control, patient M.S. homozygous for the mutation, and heterozygous parents. Arrows indicate localization of the 1031-1032insC mutation.