A novel homozygous mutation in the human <scp><i>ALG12</i></scp> gene results in an aberrant profile of oligomannose N‐glycans in patient's serum

Ziburová, Jana; Nemčovič, Marek; Šesták, Sergej; Bellová, Jana; Pakanová, Zuzana; Siváková, Barbara; Šalingová, Anna; Šebová, Claudia; Ostrožlíková, Mária; Lekka, Dimitra-Evanthia; Brucknerová, Jana; Brucknerová, Ingrid; Skokňová, Martina; Cullough, Alexandra Mc; Hrčková, Gabriela; Hlavatá, Anna; Bzdúch, Vladimír; Mucha, Ján; Baráth, Péter

doi:10.1002/ajmg.a.62474

Cited by 7 publications

(6 citation statements)

References 33 publications

(50 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus far, the majority of studies on glycomics in CDG have exploited profiling methodologies, such as MALDI‐TOF and LC‐QTOF MS. For ALG3‐CDG, increased abundance of short high‐mannose glycans were found for four patients including Man3 and Man4 structures 18 . Application in single cases revealed a lowered ratio of Man8/Man7 glycans for ALG12‐CDG, similar to the current study 19 . Standardization of methodology for absolute quantification might further aid positioning of glycomics as diagnostic test 9 .…”

Section: Discussionsupporting

confidence: 83%

“…18 Application in single cases revealed a lowered ratio of Man8/Man7 glycans for ALG12-CDG, similar to the current study. 19 Standardization of methodology for absolute quantification might further aid positioning of glycomics as diagnostic test. 9 Further validation of the potential biomarkers reported before and in the current study is necessary by the establishment of well-defined patient cohorts with standardized collection of biomaterials, consisting of sufficient number of patient samples per defect and in time.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Synergistic use of glycomics and single‐molecule molecular inversion probes for identification of congenital disorders of glycosylation type‐1

Bakar

Ashikov

Brum

et al. 2022

J of Inher Metab Disea

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Synergistic use of glycomics and single‐molecule molecular inversion probes for identification of congenital disorders of glycosylation type‐1

Bakar

Ashikov

Brum

et al. 2022

J of Inher Metab Disea

View full text Add to dashboard Cite

show abstract

“…ALG9 Mutation carriers develop kidney and liver cysts [39]. ALG12 gene pathogenic mutation results in the accumulation of GlcNAc2Man5-7 and decreased levels of GlcNAc2Man8-9 in the serum of congenital disorder of glycosylation type IgG (ALG12-CDG) patients [40,41]. Research has shown that ALG3 contributes to stemness traits in breast cancer [22].…”

Section: Discussionmentioning

confidence: 99%

High-mannose glycosylation of ITGAM regulates the development and differentiation of trophoblast in the placenta

Cui

Wang

Pei

et al. 2023

Preprint

View full text Add to dashboard Cite

Background Development of placenta and differentiation of trophoblast is a hallmark event for successful pregnancy. Trophoblast stem (TS) cells proliferate and differentiate into TS-like cytotrophoblasts (CTBs), further formulate the differentiated subtypes, syncytiotrophoblasts (STBs) and invasive extravillous tropholoblasts (EVTs). Defective differentiation of TS-like CTBs is associated with severe gestational diseases. Protein glycosylation is an essential form of posttranslational modification. However, glycosylation-related mechanism controlling TS-like CTBs differentiation remains unknown. This study aims to investigate the function of high-mannose type glycans and ALG3 on TS-like CTBs differentiation. Furthermore, the mechanism of high-mannose and ITGAM during TS-like CTBs differentiation were explored.Methods Employing lectin microarray, the glycosylation expression traits were compared in the villi of miscarriage patients and healthy women. The expression of high-mannose and ALG3 were investigated by immunoblotting and immunofluorescence assays. The glycosylation proteins were screened by pull down and LC-MS/MS detection. Signaling pathway were screened by the human phosphokinase antibody array. The differentiation of TS-like CTBs were measured by immunoblotting and immunofluorescence assays.Results Lectin microarray results revealed that increased level of high-mannose type glycans on the TS-like CTBs of miscarriage patients compared with normal pregnancy women. Meantime, ALG3 levels increased in TS-like CTBs of miscarriage patients. Upregulating high-mannose type glycans by ALG3 hampered TS-like CTBs differentiated into STBs and EVTs, and arrested TS-like CTBs in the property stage. Furthermore, high level of high-mannose type glycans on ITGAM inhibited the binding of ITGAM and Fn, inactivating the p-STAT1 signaling pathway, further inhibiting TS-like CTBs differentiation potential.Conclusions These findings reveal that high-mannose type glycans, especially on ITGAM, hampered binding of ITGAM and Fn, which leads to the impaired TS-like CTBs differentiation by p-STAT1 signaling pathway. The present study provides novel insight into the function and mechanism of α1,3-linked high-mannose type glycans in TS-like CTBs differentiation in human placenta, which can also be used as a glycol molecular target for the treatment of miscarriage.

show abstract

“…Defects in either ALG12 or MOGS compromise N-glycan biosynthesis ( 61 , 62 ). ALG12 is a mannosyltransferase responsible for adding the eighth mannose to the lipid-linked oligosaccharide precursor, whereas MOGS is a glucosidase that catalyzes the trimming of the first glucose residue from the Glc3-Man9-GlcNAc2 precursor ( Figure 2 ).…”

Section: Immunological Burden In Congenital Disorders Of Glycosylationmentioning

confidence: 99%

Revisiting the immunopathology of congenital disorders of glycosylation: an updated review

Pascoal,

Francisco,

Mexia

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

Glycosylation is a critical post-translational modification that plays a pivotal role in several biological processes, such as the immune response. Alterations in glycosylation can modulate the course of various pathologies, such as the case of congenital disorders of glycosylation (CDG), a group of more than 160 rare and complex genetic diseases. Although the link between glycosylation and immune dysfunction has already been recognized, the immune involvement in most CDG remains largely unexplored and poorly understood. In this study, we provide an update on the immune dysfunction and clinical manifestations of the 12 CDG with major immune involvement, organized into 6 categories of inborn errors of immunity according to the International Union of Immunological Societies (IUIS). The immune involvement in phosphomannomutase 2 (PMM2)-CDG - the most frequent CDG - was comprehensively reviewed, highlighting a higher prevalence of immune issues during infancy and childhood and in R141H-bearing genotypes. Finally, using PMM2-CDG as a model, we point to links between abnormal glycosylation patterns in host cells and possibly favored interactions with microorganisms that may explain the higher susceptibility to infection. Further characterizing immunopathology and unusual host-pathogen adhesion in CDG can not only improve immunological standards of care but also pave the way for innovative preventive measures and targeted glycan-based therapies that may improve quality of life for people living with CDG.

show abstract

A novel homozygous mutation in the human ALG12 gene results in an aberrant profile of oligomannose N‐glycans in patient's serum

Cited by 7 publications

References 33 publications

Synergistic use of glycomics and single‐molecule molecular inversion probes for identification of congenital disorders of glycosylation type‐1

Synergistic use of glycomics and single‐molecule molecular inversion probes for identification of congenital disorders of glycosylation type‐1

High-mannose glycosylation of ITGAM regulates the development and differentiation of trophoblast in the placenta

Revisiting the immunopathology of congenital disorders of glycosylation: an updated review

Contact Info

Product

Resources

About