Abstract
Protein glycosylation is an important post-translational modification. It enhances the functional diversity of proteins, half-life and influences their biological activity. Defective glycosylation often leads to multisystem disease and adds itself to the expanding group of ‘Congenital disorders or glycosylation’ which are predominantly disorders of N-linked glycosylation. Another rapidly growing group of disorders are defects in O-linked glycosylation, including a subset of dystroglycanopathies. Current diagnostic strategies for glycosylation disorders are compounded by the multivariate clinical phenotype of many of the diseases. Biochemical tests such as the isoelectric focusing of transferrin and apolipoprotein CIII are used to assess a patient’s glycoform profile before in depth enzyme and genetic analysis is initiated. Whilst the glycoform profiling has been instrumental in screening for many glycosylation disorders, there is a need for a more sensitive and informative test. This short review gives an overview of the recent methods used in glycobiology research that could be used to devise such a test, which alongside currently used diagnostic tests should further facilitate the delineation of CDG subtypes. It provides a view to a potential strategy using marker glycopeptides to develop a mass spectrometry based assay that could be implemented into clinical diagnostic laboratories.
Highlights
The human genome sequencing project demonstrated 30-50,000 genes, but the human ‘proteome’ shows we have > 500,000 proteins [1]
The reason for the discrepancy between genes and proteins encoded for is from a higher order of complexity of protein products due to ‘post translational modifications’ (PTMs)
Analysis of the genetic code of a protein cannot predict this; several diseases require further characterisation by other means such as mass spectrometry to help understand the cause of the malfunction of a protein
Summary
The human genome sequencing project demonstrated 30-50,000 genes, but the human ‘proteome’ shows we have > 500,000 proteins [1]. In depth analysis of the glycans from CDG patients has conventionally been performed using Matrix Assisted Laser Desorption Ionisation Time of Flight Mass Spectrometry (MALDI ToF MS) This established method involves the removal of the N-linked glycans from glycoproteins either chemically or enzymatically. Recent further technical advances in mass spectrometry such as MALDI ion trap profiling have allowed sequencing of glycans that reveal detailed information on glycan structures thereby distinguishing between primary genetic defects in the N-glycosylation process, Golgitrafficking disorders, and secondary causes of underglycosylation [25]. Using this approach they were able to identify multiple glycan compositions at each individual glycosylation site and thereby improve the determination of glycan microheterogeneity by mass spectrometry
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
