Platelet Membrane Glycoprofiling in a PMM2-CDG Patient
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Journal of Inborn Errors of Metabolism and Screening |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S2326-45942021000100323 |
Resumo: | Abstract Congenital disorders of glycosylation (CDG) are metabolic hereditary diseases caused by defects in the synthesis of glycoconjugates. CDG have been described in sugar-nucleotide biosynthesis and transporter, glycosyltransferases, vesicular transport, as well as in lipid biosynthesis and glycosylphosphatidylinositol anchors. PMM2-CDG is caused by mutations in the phosphomannomutase-2 (PMM2) gene and shows autosomal recessive inheritance. It affects all organs and tissues, ranging from severe psychomotor retardation to moderate intellectual disability. Alterations in the primary haemostatic system have been reported in these patients and they can lead to severe bleeding or excessive thrombosis with subsequent vascular insufficiency. Despite of being the most common CDG, platelet glycosylation and sialylation defects in PMM2-CDG patients remain incompletely characterized. In this study, we applied a lectin-based flow cytometry approach to report the first characterization of the highly glycosylated platelet membrane glycan profile in a PMM2-CDG patient. In the PMM2-CDG patient’s platelet samples, a decreased binding of SNA lectin, indicative of reduced terminal α-2-6 sialic acid content, and an increased binding of PNA lectin, suggesting desialylation of β-1-N-acetylgalactosamine residues, were observed. Reduced expression of terminal sialic acids in platelet membrane glycoproteins may contribute to the increased risk of hemorrhage reported in these patients by promoting platelet clearance and thrombocytopenia. |
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Journal of Inborn Errors of Metabolism and Screening |
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Platelet Membrane Glycoprofiling in a PMM2-CDG Patientmass spectrometryplatelet membraneglycoprofilePMM2-CDGcongenital disorders of glycosylationAbstract Congenital disorders of glycosylation (CDG) are metabolic hereditary diseases caused by defects in the synthesis of glycoconjugates. CDG have been described in sugar-nucleotide biosynthesis and transporter, glycosyltransferases, vesicular transport, as well as in lipid biosynthesis and glycosylphosphatidylinositol anchors. PMM2-CDG is caused by mutations in the phosphomannomutase-2 (PMM2) gene and shows autosomal recessive inheritance. It affects all organs and tissues, ranging from severe psychomotor retardation to moderate intellectual disability. Alterations in the primary haemostatic system have been reported in these patients and they can lead to severe bleeding or excessive thrombosis with subsequent vascular insufficiency. Despite of being the most common CDG, platelet glycosylation and sialylation defects in PMM2-CDG patients remain incompletely characterized. In this study, we applied a lectin-based flow cytometry approach to report the first characterization of the highly glycosylated platelet membrane glycan profile in a PMM2-CDG patient. In the PMM2-CDG patient’s platelet samples, a decreased binding of SNA lectin, indicative of reduced terminal α-2-6 sialic acid content, and an increased binding of PNA lectin, suggesting desialylation of β-1-N-acetylgalactosamine residues, were observed. Reduced expression of terminal sialic acids in platelet membrane glycoproteins may contribute to the increased risk of hemorrhage reported in these patients by promoting platelet clearance and thrombocytopenia.Latin American Society Inborn Errors and Neonatal Screening (SLEIMPN); Instituto Genética para Todos (IGPT)2021-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S2326-45942021000100323Journal of Inborn Errors of Metabolism and Screening v.9 2021reponame:Journal of Inborn Errors of Metabolism and Screeninginstname:Instituto Genética para Todos (IGPT)instacron:IGPT10.1590/2326-4594-jiems-2020-0030info:eu-repo/semantics/openAccessPapazoglu,G.M.Ruiz,S.M. SilveraSalinas,R.Pereira,M.I.Cubilla,M.A.Pesaola,F.Ghione,S.Ramadán,N.Martinez-Duncker,I.Asteggiano,C.G.eng2021-08-25T00:00:00Zoai:scielo:S2326-45942021000100323Revistahttp://jiems-journal.org/ONGhttps://old.scielo.br/oai/scielo-oai.phpjiems@jiems-journal.org||rgiugliani@hcpa.edu.br2326-45942326-4594opendoar:2021-08-25T00:00Journal of Inborn Errors of Metabolism and Screening - Instituto Genética para Todos (IGPT)false |
dc.title.none.fl_str_mv |
Platelet Membrane Glycoprofiling in a PMM2-CDG Patient |
title |
Platelet Membrane Glycoprofiling in a PMM2-CDG Patient |
spellingShingle |
Platelet Membrane Glycoprofiling in a PMM2-CDG Patient Papazoglu,G.M. mass spectrometry platelet membrane glycoprofile PMM2-CDG congenital disorders of glycosylation |
title_short |
Platelet Membrane Glycoprofiling in a PMM2-CDG Patient |
title_full |
Platelet Membrane Glycoprofiling in a PMM2-CDG Patient |
title_fullStr |
Platelet Membrane Glycoprofiling in a PMM2-CDG Patient |
title_full_unstemmed |
Platelet Membrane Glycoprofiling in a PMM2-CDG Patient |
title_sort |
Platelet Membrane Glycoprofiling in a PMM2-CDG Patient |
author |
Papazoglu,G.M. |
author_facet |
Papazoglu,G.M. Ruiz,S.M. Silvera Salinas,R. Pereira,M.I. Cubilla,M.A. Pesaola,F. Ghione,S. Ramadán,N. Martinez-Duncker,I. Asteggiano,C.G. |
author_role |
author |
author2 |
Ruiz,S.M. Silvera Salinas,R. Pereira,M.I. Cubilla,M.A. Pesaola,F. Ghione,S. Ramadán,N. Martinez-Duncker,I. Asteggiano,C.G. |
author2_role |
author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Papazoglu,G.M. Ruiz,S.M. Silvera Salinas,R. Pereira,M.I. Cubilla,M.A. Pesaola,F. Ghione,S. Ramadán,N. Martinez-Duncker,I. Asteggiano,C.G. |
dc.subject.por.fl_str_mv |
mass spectrometry platelet membrane glycoprofile PMM2-CDG congenital disorders of glycosylation |
topic |
mass spectrometry platelet membrane glycoprofile PMM2-CDG congenital disorders of glycosylation |
description |
Abstract Congenital disorders of glycosylation (CDG) are metabolic hereditary diseases caused by defects in the synthesis of glycoconjugates. CDG have been described in sugar-nucleotide biosynthesis and transporter, glycosyltransferases, vesicular transport, as well as in lipid biosynthesis and glycosylphosphatidylinositol anchors. PMM2-CDG is caused by mutations in the phosphomannomutase-2 (PMM2) gene and shows autosomal recessive inheritance. It affects all organs and tissues, ranging from severe psychomotor retardation to moderate intellectual disability. Alterations in the primary haemostatic system have been reported in these patients and they can lead to severe bleeding or excessive thrombosis with subsequent vascular insufficiency. Despite of being the most common CDG, platelet glycosylation and sialylation defects in PMM2-CDG patients remain incompletely characterized. In this study, we applied a lectin-based flow cytometry approach to report the first characterization of the highly glycosylated platelet membrane glycan profile in a PMM2-CDG patient. In the PMM2-CDG patient’s platelet samples, a decreased binding of SNA lectin, indicative of reduced terminal α-2-6 sialic acid content, and an increased binding of PNA lectin, suggesting desialylation of β-1-N-acetylgalactosamine residues, were observed. Reduced expression of terminal sialic acids in platelet membrane glycoproteins may contribute to the increased risk of hemorrhage reported in these patients by promoting platelet clearance and thrombocytopenia. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-01-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S2326-45942021000100323 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S2326-45942021000100323 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/2326-4594-jiems-2020-0030 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Latin American Society Inborn Errors and Neonatal Screening (SLEIMPN); Instituto Genética para Todos (IGPT) |
publisher.none.fl_str_mv |
Latin American Society Inborn Errors and Neonatal Screening (SLEIMPN); Instituto Genética para Todos (IGPT) |
dc.source.none.fl_str_mv |
Journal of Inborn Errors of Metabolism and Screening v.9 2021 reponame:Journal of Inborn Errors of Metabolism and Screening instname:Instituto Genética para Todos (IGPT) instacron:IGPT |
instname_str |
Instituto Genética para Todos (IGPT) |
instacron_str |
IGPT |
institution |
IGPT |
reponame_str |
Journal of Inborn Errors of Metabolism and Screening |
collection |
Journal of Inborn Errors of Metabolism and Screening |
repository.name.fl_str_mv |
Journal of Inborn Errors of Metabolism and Screening - Instituto Genética para Todos (IGPT) |
repository.mail.fl_str_mv |
jiems@jiems-journal.org||rgiugliani@hcpa.edu.br |
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1754732520274919424 |