Use of Endoglycosidase H as a diagnostic tool for MAN1B1‐CDG patients

Duvet, Sandrine; Mouajjah, Dounia; Péanne, Romain; Matthijs, Gert; Raymond, Kimiyo; Jaeken, Jaak; Morava, Éva; Foulquier, François

doi:10.1002/elps.201800020

Cited by 10 publications

(6 citation statements)

References 21 publications

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“…Although specific, those N-glycan species occur at trace levels in serum (<10% when summing all the PNGase-released species), which corroborates the intriguing involvement of a limited number of circulating N-glycoproteins. By hydrolyzing Endo H-released N-glycans with mannosidases, Duvet et al demonstrated that MAN1B1-specific hybrid N-glycans have isomeric structures different from those present in control samples, with α1,2 linked mannose residues [ 10 ]. Recently an alternative MS-based strategy involving the analysis of Rapifluor-derivatized PNGase F-released N-glycans, Messina et al [ 17 ] confirmed these findings in MAN1B1-CDG individuals.…”

Section: Discussionmentioning

confidence: 99%

“…To overcome these drawbacks, alternative strategies (more or less accessible in clinical settings) have been proposed such as targeted analysis of immunopurified Trf and/or IgG [ 4 , 9 ] as well as the convenient detection of high-mannose and hybrid-type N-glycans following Endo-β- N -acetylglucosaminidase (Endo H) serum treatment. Indeed, Duvet et al [ 10 ] reported unambiguous profiles of Endo H-released serum N-glycans for seven MAN1B1-CDG patients with clear accumulation of oligosaccharidic structures harboring 4–5 Man residues.…”

Section: Introductionmentioning

confidence: 99%

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MAN1B1-CDG: Three new individuals and associated biochemical profiles

Sakhi¹,

Cholet²,

Wehbi³

et al. 2021

Molecular Genetics and Metabolism Reports

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Congenital disorders of glycosylation (CDG) constitute an ever-growing group of genetic diseases affecting the glycosylation of proteins. CDG individuals usually present with severe multisystem disorders. MAN1B1-CDG is a CDG with nonspecific clinical symptoms such as intellectual deficiency and developmental delay. Although up to 40 affected individuals were described so far, its final diagnosis is not straightforward using common biochemical methods due to the trace-level accumulation of defective glycan structures. In this study, we present three unreported MAN1B1-CDG individuals and propose a decision tree to reach diagnosis using a panel of techniques ranging from exome sequencing to gel electrophoresis and mass spectrometry. The occurrence of MAN1B1-CDG in patients showing unexplained intellectual disability and development delay, as well as a particular transferrin glycosylation profile, can be ascertained notably using matrix assisted laser desorption/ionization – time of flight (MALDI-TOF) mass spectrometry analysis of endo -β-acetylglucosaminidase H-released serum N-glycans. In addition to reporting new pathogenic variants and additional clinical signs such as hypersialorrhea, we highlight particular biochemical features of MAN1B1-CDG with potential glycoprotein-specific glycosylation defects.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MAN1B1-CDG: Three new individuals and associated biochemical profiles

Sakhi¹,

Cholet²,

Wehbi³

et al. 2021

Molecular Genetics and Metabolism Reports

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“…N ‐glycans were prepared and released by PNGase F from an aliquot of 20 μL of serum as previously described 17 . Released glycans were then permethylated, extracted and purified on a Sep‐Pak column as previously described 18 .…”

Section: Methodsmentioning

confidence: 99%

Variation of the serum N‐glycosylation during the pregnancy of a MPI‐CDG patient

et al. 2021

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For the first time the glycosylation of a patient with a MPI‐CDG during pregnancy is monitored. MPI‐CDG, is characterised by a deficiency in mannose‐6‐phosphate isomerase (MPI) leading to a reduced pool of glycosylation precursors, impairing the biosynthesis of N‐glycans leading to N‐glycosylation defects. The abnormal N‐glycosylation profile with an elevation of asialotransferrin and disialotransferrin, typical of CDG type I, is assessable by transferrin isoelectrofocusing. Oral D‐mannose supplementation for MPI‐CDG patients has been widely used and improves clinical manifestations. The glycosylation of a MPI‐CDG patient during pregnancy without mannose supplementation was studied using carbohydrate deficient transferrin (CDT) assay, transferrin isoelectrofocusing (IEF) and mass spectrometry of total serum N‐glycans. A general improvement of the glycosylation profile of the patient due to a better transfer of the glycan precursors as well as an increase of the triantennary glycans (and sialylation) was observed. In conclusion, in the absence of mannose supplementation, the previously observed glycosylation abnormality of the MPI‐CDG patient was corrected. The molecular mechanism underlying this N‐glycosylation rescue during MPI‐CDG pregnancy further needs to be investigated.

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“…Early in 2013, MALDI-TOF/TOF (Applied Biosystems 4800) was applied to profile the permethylated glycans derived from congenital disorders of glycosylation (CDGs) patient sera and proved to be able to differentiate CDG from controls ( Xia et al, 2013 ). Recently, Duvet et al (2018) investigated the serum N-glycome expressions in MAN1B1-CDG patients using the same MAIDI-TOF/TOF system in combination with an Endo-β-N-acetylglucosaminidase H (Endo H) digestion. Since the Endo H can only release high-mannose and hybrid structures, a straightforward investigation of MAN1B1 deficit was achieved.…”

Section: Mass Spectrometry-based Separation Techniques Facilitate Gly...mentioning

confidence: 99%

MS-based glycomics: An analytical tool to assess nervous system diseases

et al. 2022

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Neurological diseases affect millions of peopleochemistryorldwide and are continuously increasing due to the globe’s aging population. Such diseases affect the nervous system and are characterized by a progressive decline in brain function and progressive cognitive impairment, decreasing the quality of life for those with the disease as well as for their families and loved ones. The increased burden of nervous system diseases demands a deeper insight into the biomolecular mechanisms at work during disease development in order to improve clinical diagnosis and drug design. Recently, evidence has related glycosylation to nervous system diseases. Glycosylation is a vital post-translational modification that mediates many biological functions, and aberrant glycosylation has been associated with a variety of diseases. Thus, the investigation of glycosylation in neurological diseases could provide novel biomarkers and information for disease pathology. During the last decades, many techniques have been developed for facilitation of reliable and efficient glycomic analysis. Among these, mass spectrometry (MS) is considered the most powerful tool for glycan analysis due to its high resolution, high sensitivity, and the ability to acquire adequate structural information for glycan identification. Along with MS, a variety of approaches and strategies are employed to enhance the MS-based identification and quantitation of glycans in neurological samples. Here, we review the advanced glycomic tools used in nervous system disease studies, including separation techniques prior to MS, fragmentation techniques in MS, and corresponding strategies. The glycan markers in common clinical nervous system diseases discovered by utilizing such MS-based glycomic tools are also summarized and discussed.

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Use of Endoglycosidase H as a diagnostic tool for MAN1B1‐CDG patients

Cited by 10 publications

References 21 publications

MAN1B1-CDG: Three new individuals and associated biochemical profiles

MAN1B1-CDG: Three new individuals and associated biochemical profiles

Variation of the serum N‐glycosylation during the pregnancy of a MPI‐CDG patient

MS-based glycomics: An analytical tool to assess nervous system diseases

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