UNIT 17.4 Detection of Hypo-N-Glycosylation Using Mass Spectrometry of Transferrin

  1. John F. O'Brien,
  2. Jean M. Lacey,
  3. H. Robert Bergen III

Published Online: 1 JUL 2007

DOI: 10.1002/0471142905.hg1704s54

Current Protocols in Human Genetics

Current Protocols in Human Genetics

How to Cite

O'Brien, J. F., Lacey, J. M. and Bergen, H. R. 2007. Detection of Hypo-N-Glycosylation Using Mass Spectrometry of Transferrin. Current Protocols in Human Genetics. 54:17.4:17.4.1–17.4.9.

Author Information

  1. Mayo Clinic College of Medicine, Rochester, Minnesota

Publication History

  1. Published Online: 1 JUL 2007
  2. Published Print: JUL 2007


Many congenital disorders of glycosylation (CDG) can be diagnosed by observing the extent of glycosylation of the abundant serum glycoprotein transferrin (Trf). Trf is an N-glycosylated protein with two asparagine glycation sites. CDG types I are those genetic defects which occur prior to transfer of the complex oligosaccharide to the acceptor asparagine in the cotranslated polypeptide chain. CDG Ia constitutes by far the most frequent form of CDG and is the result of mutations in the phosphomannomutase gene. CDG Ia and the Ib subtype (Phosphomannoisomerase deficiency) result in low cellular mannose-1-phosphate levels, a required precursor for oligosaccharide assembly in the endoplasmic reticulum. The deficiency in oligosaccharides with branched mannose structures is thereafter expressed by the appearance of glycoproteins with unoccupied N-glycosylation sites (hypoglycosylation). Currently, there have been at least 11 Type I defects, type Ia being by far the most frequently occurring. Most, if not all type I defects result in unoccupied N-glycation sites. Hypoglycosylated Trf, also known as carbohydrate-deficient Trf (CDT), can be detected using mass spectrometry (MS) to measure the masses of the serum Trf. The methods for sample preparation using affinity chromatography and MS analysis are described in this unit. Curr. Protoc. Hum. Genet. 54:17.4.1-17.4.9 © 2007 by John Wiley & Sons, Inc.


  • congenital disorders of glycosylation (CDG);
  • carbohydrate deficient Transferrin (CDT) or hypoglycosylated tranferrin;
  • transferrin (Trf);
  • glycoforms;
  • glycoproteins;
  • oligosaccharides