<i>N</i>-Glycoprofiling of SLC35A2-CDG: Patient with a Novel Hemizygous Variant
Congenital disorders of glycosylation (CDG) are a group of rare inherited metabolic disorders caused by a defect in the process of protein glycosylation. In this work, we present a comprehensive glycoprofile analysis of a male patient with a novel missense variant in the <i>SLC35A2</i> g...
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MDPI AG
2023-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/2/580 |
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| author | Rebeka Kodríková Zuzana Pakanová Maroš Krchňák Mária Šedivá Sergej Šesták Filip Květoň Gábor Beke Anna Šalingová Katarína Skalická Katarína Brennerová Emília Jančová Peter Baráth Ján Mucha Marek Nemčovič |
| author_facet | Rebeka Kodríková Zuzana Pakanová Maroš Krchňák Mária Šedivá Sergej Šesták Filip Květoň Gábor Beke Anna Šalingová Katarína Skalická Katarína Brennerová Emília Jančová Peter Baráth Ján Mucha Marek Nemčovič |
| author_sort | Rebeka Kodríková |
| collection | DOAJ |
| description | Congenital disorders of glycosylation (CDG) are a group of rare inherited metabolic disorders caused by a defect in the process of protein glycosylation. In this work, we present a comprehensive glycoprofile analysis of a male patient with a novel missense variant in the <i>SLC35A2</i> gene, coding a galactose transporter that translocates UDP-galactose from the cytosol to the lumen of the endoplasmic reticulum and Golgi apparatus. Isoelectric focusing of serum transferrin, which resulted in a CDG type II pattern, was followed by structural analysis of transferrin and serum <i>N</i>-glycans, as well as the analysis of apolipoprotein CIII <i>O</i>-glycans by mass spectrometry. An abnormal serum <i>N</i>-glycoprofile with significantly increased levels of agalactosylated (Hex3HexNAc4-5 and Hex3HexNAc5Fuc1) and monogalactosylated (Hex4HexNAc4 ± NeuAc1) <i>N</i>-glycans was observed. Additionally, whole exome sequencing and Sanger sequencing revealed de novo hemizygous c.461T > C (p.Leu154Pro) mutation in the <i>SLC35A2</i> gene. Based on the combination of biochemical, analytical, and genomic approaches, the set of distinctive <i>N</i>-glycan biomarkers was characterized. Potentially, the set of identified aberrant <i>N</i>-glycans can be specific for other variants causing SLC35A2-CDG and can distinguish this disorder from the other CDGs or other defects in the galactose metabolism. |
| first_indexed | 2024-03-11T09:07:15Z |
| format | Article |
| id | doaj.art-b8f285849fce43669acafaebbecacf11 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T09:07:15Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-b8f285849fce43669acafaebbecacf112023-11-16T19:20:20ZengMDPI AGBiomedicines2227-90592023-02-0111258010.3390/biomedicines11020580<i>N</i>-Glycoprofiling of SLC35A2-CDG: Patient with a Novel Hemizygous VariantRebeka Kodríková0Zuzana Pakanová1Maroš Krchňák2Mária Šedivá3Sergej Šesták4Filip Květoň5Gábor Beke6Anna Šalingová7Katarína Skalická8Katarína Brennerová9Emília Jančová10Peter Baráth11Ján Mucha12Marek Nemčovič13Institute of Chemistry, Centre of Glycomics, Slovak Academy of Sciences, Dúbravská cesta 9, 841 04 Bratislava, SlovakiaInstitute of Chemistry, Centre of Glycomics, Slovak Academy of Sciences, Dúbravská cesta 9, 841 04 Bratislava, SlovakiaInstitute of Chemistry, Centre of Glycomics, Slovak Academy of Sciences, Dúbravská cesta 9, 841 04 Bratislava, SlovakiaInstitute of Chemistry, Centre of Glycomics, Slovak Academy of Sciences, Dúbravská cesta 9, 841 04 Bratislava, SlovakiaInstitute of Chemistry, Centre of Glycomics, Slovak Academy of Sciences, Dúbravská cesta 9, 841 04 Bratislava, SlovakiaInstitute of Chemistry, Centre of Glycomics, Slovak Academy of Sciences, Dúbravská cesta 9, 841 04 Bratislava, SlovakiaInstitute of Chemistry, Centre of Glycomics, Slovak Academy of Sciences, Dúbravská cesta 9, 841 04 Bratislava, SlovakiaNational Institute of Children’s Diseases, Center for Inherited Metabolic Disorders, Limbová 1, 833 40 Bratislava, SlovakiaLaboratory of Clinical and Molecular Genetics, National Institute of Children’s Diseases, Limbová 1, 833 40 Bratislava, SlovakiaDepartment of Paediatrics, Faculty of Medicine of Comenius University and National Institute for Children’s Diseases, Limbová 1, 833 40 Bratislava, SlovakiaDepartment of Paediatrics, Faculty of Medicine of Comenius University and National Institute for Children’s Diseases, Limbová 1, 833 40 Bratislava, SlovakiaInstitute of Chemistry, Centre of Glycomics, Slovak Academy of Sciences, Dúbravská cesta 9, 841 04 Bratislava, SlovakiaInstitute of Chemistry, Centre of Glycomics, Slovak Academy of Sciences, Dúbravská cesta 9, 841 04 Bratislava, SlovakiaInstitute of Chemistry, Centre of Glycomics, Slovak Academy of Sciences, Dúbravská cesta 9, 841 04 Bratislava, SlovakiaCongenital disorders of glycosylation (CDG) are a group of rare inherited metabolic disorders caused by a defect in the process of protein glycosylation. In this work, we present a comprehensive glycoprofile analysis of a male patient with a novel missense variant in the <i>SLC35A2</i> gene, coding a galactose transporter that translocates UDP-galactose from the cytosol to the lumen of the endoplasmic reticulum and Golgi apparatus. Isoelectric focusing of serum transferrin, which resulted in a CDG type II pattern, was followed by structural analysis of transferrin and serum <i>N</i>-glycans, as well as the analysis of apolipoprotein CIII <i>O</i>-glycans by mass spectrometry. An abnormal serum <i>N</i>-glycoprofile with significantly increased levels of agalactosylated (Hex3HexNAc4-5 and Hex3HexNAc5Fuc1) and monogalactosylated (Hex4HexNAc4 ± NeuAc1) <i>N</i>-glycans was observed. Additionally, whole exome sequencing and Sanger sequencing revealed de novo hemizygous c.461T > C (p.Leu154Pro) mutation in the <i>SLC35A2</i> gene. Based on the combination of biochemical, analytical, and genomic approaches, the set of distinctive <i>N</i>-glycan biomarkers was characterized. Potentially, the set of identified aberrant <i>N</i>-glycans can be specific for other variants causing SLC35A2-CDG and can distinguish this disorder from the other CDGs or other defects in the galactose metabolism.https://www.mdpi.com/2227-9059/11/2/580congenital disorders of glycosylationglycoprofilingSLC35A2-CDG |
| spellingShingle | Rebeka Kodríková Zuzana Pakanová Maroš Krchňák Mária Šedivá Sergej Šesták Filip Květoň Gábor Beke Anna Šalingová Katarína Skalická Katarína Brennerová Emília Jančová Peter Baráth Ján Mucha Marek Nemčovič <i>N</i>-Glycoprofiling of SLC35A2-CDG: Patient with a Novel Hemizygous Variant Biomedicines congenital disorders of glycosylation glycoprofiling SLC35A2-CDG |
| title | <i>N</i>-Glycoprofiling of SLC35A2-CDG: Patient with a Novel Hemizygous Variant |
| title_full | <i>N</i>-Glycoprofiling of SLC35A2-CDG: Patient with a Novel Hemizygous Variant |
| title_fullStr | <i>N</i>-Glycoprofiling of SLC35A2-CDG: Patient with a Novel Hemizygous Variant |
| title_full_unstemmed | <i>N</i>-Glycoprofiling of SLC35A2-CDG: Patient with a Novel Hemizygous Variant |
| title_short | <i>N</i>-Glycoprofiling of SLC35A2-CDG: Patient with a Novel Hemizygous Variant |
| title_sort | i n i glycoprofiling of slc35a2 cdg patient with a novel hemizygous variant |
| topic | congenital disorders of glycosylation glycoprofiling SLC35A2-CDG |
| url | https://www.mdpi.com/2227-9059/11/2/580 |
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