Transferrin mutations at the glycosylation site complicate diagnosis of congenital disorders of glycosylation type I
| Autor: | Alice Janssen, Lambertus P. van den Heuvel, Maïlys Guillard, Eva Morava, Nina Ondruskova, Hana Hansikova, Jiri Zeman, Machiko Kadoya, Isao Yuasa, Katerina Vesela, Ron A. Wevers, Yoshinao Wada, Dirk J. Lefeber |
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| Rok vydání: | 2011 |
| Předmět: |
Male
congenital hereditary and neonatal diseases and abnormalities Glycosylation Genomic disorders and inherited multi-system disorders Energy and redox metabolism [IGMD 3] Peptide Neuroinformatics [DCN 3] CDG - an update medicine.disease_cause Renal disorder Energy and redox metabolism [IGMD 9] Models Biological Genomic disorders and inherited multi-system disorders [IGMD 3] chemistry.chemical_compound Congenital Disorders of Glycosylation Catalytic Domain Genetics medicine Humans Genetics(clinical) Child Genetics (clinical) chemistry.chemical_classification Mutation biology Isoelectric focusing Transferrin Mitochondrial medicine Energy and redox metabolism [IGMD 8] Glycostation disorders [IGMD 4] Molecular biology Human genetics Renal disorder Membrane transport and intracellular motility [IGMD 9] Isoelectric point chemistry Biochemistry Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization biology.protein Isoelectric Focusing Perception and Action Glycostation disorders [DCN 1] Protein Processing Post-Translational Neuraminidase |
| Zdroj: | Journal of Inherited Metabolic Disease Journal of Inherited Metabolic Disease, 34, 4, pp. 901-6 Journal of Inherited Metabolic Disease, 34, 901-6 |
| ISSN: | 1573-2665 0141-8955 |
| DOI: | 10.1007/s10545-011-9311-y |
| Popis: | Item does not contain fulltext Congenital disorders of glycosylation (CDG) form a group of metabolic disorders caused by deficient glycosylation of proteins and/or lipids. Isoelectric focusing (IEF) of serum transferrin is the most common screening method to detect abnormalities of protein N-glycosylation. On the basis of the IEF profile, patients can be grouped into CDG type I or CDG type II. Several protein variants of transferrin are known that result in a shift in isoelectric point (pI). In some cases, these protein variants co-migrate with transferrin glycoforms, which complicates interpretation. In two patients with abnormal serum transferrin IEF profiles, neuraminidase digestion and subsequent IEF showed profiles suggestive of the diagnosis of CDG type I. Mass spectrometry of tryptic peptides of immunopurified transferrin, however, revealed a novel mutation at the N-glycan attachment site. In case 1, a peptide with mutation p.Asn630Thr in the 2nd glycosylation site was identified, resulting in an additional band at disialotransferrin position on IEF. After neuraminidase digestion, a single band was found at the asialotransferrin position, indistinguishable from CDG type I patients. In case 2, a peptide with mutation p.Asn432His was found. These results show the use of mass spectrometry of transferrin peptides in the diagnostic track of CDG type I. |
| Databáze: | OpenAIRE |
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