title: Mass spectrometry of transferrin and apolipoprotein C-III for diagnosis and screening of congenital disorder of glycosylation.
abstract: Congenital disorder of glycosylation (CDG), formerly representing a group of diseases due to defects in the biosynthetic pathway of protein N-glycosylation, currently covers a wide range of disorders affecting glycoconjugates. Since its first application to serum transferrin from a CDG patient with phosphomannomutase-2 deficiency in 1992, mass spectrometry (MS) has been playing a key role in identification and characterization of glycosylation defects affecting glycoproteins. MS of native transferrin detects a lack of glycans characteristic to the classical CDG-I type of molecular abnormality. Electrospray ionization MS of native transferrin, especially, allows glycoforms to be analyzed precisely but requires basic knowledge regarding deconvolution of multiply-charged ions which may generate ghost signals upon transformation into a singly-charged form. MS of glycopeptides from tryptic digestion of transferrin delineates site-specific glycoforms and reveals a delicate balance of donor/acceptor substrates or the conformational effect of nascent proteins in cells. Matrix-assisted laser desorption ionization MS of apolipoprotein C-III is a simple method of elucidating the profiles of mucin-type core 1 O-glycans including site occupancy and glycoforms. In this technological review, the principle and pitfalls of MS for CDG are discussed and mass spectra of various types of CDG are presented.
authors.affiliation: Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan. waday@mch.pref.osaka.jp.
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Wada
mesh_terms: D053305:Apolipoprotein C-III / Q000737:chemistry*; D018981:Congenital Disorders of Glycosylation / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D014168:Transferrin / Q000737:chemistry*
chemical_list: D053305:Apolipoprotein C-III; D014168:Transferrin
keywords: Apolipoprotein C3; Congenital disorder of glycosylation; Mass spectrometry; Transferrin