The impact of mass spectrometry in the diagnosis of congenital disorders of glycosylation

Sturiale, Luisa; Barone, Rita; Garozzo, Domenico

doi:10.1007/s10545-011-9306-8

Cited by 48 publications

(38 citation statements)

References 65 publications

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“…After PNGase treatment, the released N-glycans were purified by solid-phase extraction and permethylated in the presence of sodium hydroxide. The permethylated glycans were analyzed by MALDI-TOF MS in negative and positive ion mode [20,21]. …”

Section: Methodsmentioning

confidence: 99%

COG5-CDG: expanding the clinical spectrum

Rymen

Keldermans

Race

et al. 2012

Orphanet J Rare Dis

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BackgroundThe Conserved Oligomeric Golgi (COG) complex is involved in the retrograde trafficking of Golgi components, thereby affecting the localization of Golgi glycosyltransferases. Deficiency of a COG-subunit leads to defective protein glycosylation, and thus Congenital Disorders of Glycosylation (CDG). Mutations in subunits 1, 4, 5, 6, 7 and 8 have been associated with CDG-II. The first patient with COG5-CDG was recently described (Paesold-Burda et al. Hum Mol Genet 2009; 18:4350–6). Contrary to most other COG-CDG cases, the patient presented a mild/moderate phenotype, i.e. moderate psychomotor retardation with language delay, truncal ataxia and slight hypotonia.MethodsCDG-IIx patients from our database were screened for mutations in COG5. Clinical data were compared. Brefeldin A treatment of fibroblasts and immunoblotting experiments were performed to support the diagnosis.Results and conclusionWe identified five new patients with proven COG5 deficiency. We conclude that the clinical picture is not always as mild as previously described. It rather comprises a broad spectrum with phenotypes ranging from mild to very severe. Interestingly, on a clinical basis some of the patients present a significant overlap with COG7-CDG, a finding which can probably be explained by subunit interactions at the protein level.

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Section: Methodsmentioning

confidence: 99%

COG5-CDG: expanding the clinical spectrum

Rymen

Keldermans

Race

et al. 2012

Orphanet J Rare Dis

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“…Because these defective genes affect proteins in a variety of functionally diverse metabolic pathways, the clinical presentation can vary, making differentiation between CDG subtypes quite challenging. Currently, diagnostic tests for CDG are limited to electrophoresis or MS-based tests that characterize the various glycoforms of transferrin [19,111]. CDG-I mutations are diagnosed by the presence of transferrin with unoccupied glycosylation sites, whereas CDG-II defects are characterized by the presence of transferrin with immature, truncated glycans [19].…”

Section: Congenital Disorders Of Glycosylationmentioning

confidence: 99%

Inflammatory glycoproteins in cardiometabolic disorders, autoimmune diseases and cancer

Connelly

Gruppen

Otvos

et al. 2016

Clinica Chimica Acta

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The physiological function initially attributed to the oligosaccharide moieties or glycans on inflammatory glycoproteins was to improve protein stability. However, it is now clear that glycans play a prominent role in glycoprotein structure and function and in some cases contribute to disease states. In fact, glycan processing contributes to pathogenicity not only in autoimmune disorders but also in atherosclerotic cardiovascular disease, diabetes and malignancy. While most clinical laboratory tests measure circulating levels of inflammatory proteins, newly developed diagnostic and prognostic tests are harvesting the information that can be gleaned by measuring the amount or structure of the attached glycans, which may be unique to individuals as well as various diseases. As such, these newer glycan-based tests may provide future means for more personalized approaches to patient stratification and improved patient care. Here we will discuss recent progress in high-throughput laboratory methods for glycomics (i.e. the study of glycan structures) and glycoprotein quantification by methods such as mass spectrometry and nuclear magnetic resonance spectroscopy. We will also review the clinical utility of glycoprotein and glycan measurements in the prediction of common low-grade inflammatory disorders including cardiovascular disease, diabetes and cancer, as well as for monitoring autoimmune disease activity.

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“…Because a glycoprotein may have PO glycosites, or the degree of occupancy of a specific glycosite may change with pathological conditions, such as type I congenital disorders of glycosylation (39,40), quantifying a glycoprotein using only the sugar-occupied portion may lead to inaccurate quantification. Accordingly, many have reported that changes or variations in protein expression and glycosylation occupancy may not always be analogous or parallel (41,42).…”

Section: Discussionmentioning

confidence: 99%

The GlycoFilter: A Simple and Comprehensive Sample Preparation Platform for Proteomics, N-Glycomics and Glycosylation Site Assignment

Zhou

Froehlich

Briscoe

et al. 2013

Molecular & Cellular Proteomics

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Current strategies to study N-glycoproteins in complex samples are often discrete, focusing on either N-glycans or N-glycosites enriched by sugar-based techniques. In this study we report a simple and rapid sample preparation platform, the GlycoFilter, which allows a comprehensive characterization of N-glycans, N-glycosites, and proteins in a single workflow. Both PNGase F catalyzed de-N-glycosylation and trypsin digestions are accelerated by microwave irradiation and performed sequentially in a single spin filter. Both N-glycans and peptides (including de-N-glycosylated peptides) are separately collected by filtration. The condition to effectively collect complex and heterogeneous N-glycans was established on model glycoproteins, bovine ribonuclease B, bovine fetuin, and human serum IgG. With this platform, the N-glycome, Nglycoproteome and proteome of human urine and plasma were characterized. Overall, a total of 865 and 295 Nglycosites were identified from three pairs of urine and plasma samples, respectively. Many sites were defined unambiguously as partially occupied by the detection of their nonsugar-modified peptides (128 from urine and 61 from plasma), demonstrating that partial occupancy of N-glycosylation occurs frequently. Given the likely high prevalence and variability of partial occupancy, glycoprotein quantification based exclusively on deglycosylated peptides may lead to inaccurate quantification. Molecular

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The impact of mass spectrometry in the diagnosis of congenital disorders of glycosylation

Cited by 48 publications

References 65 publications

COG5-CDG: expanding the clinical spectrum

COG5-CDG: expanding the clinical spectrum

Inflammatory glycoproteins in cardiometabolic disorders, autoimmune diseases and cancer

The GlycoFilter: A Simple and Comprehensive Sample Preparation Platform for Proteomics, N-Glycomics and Glycosylation Site Assignment

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