Keeping an eye on congenital disorders of O-glycosylation: a systematic literature review

Francisco, Rita; Pascoal, Carlota; Marques‐da‐Silva, Dorinda; Morava, Éva; Gole, Glen A.; Coman, David; Jaeken, Jaak; Ferreira, Vanessa

doi:10.1007/s10545-017-0119-2

Cited by 7 publications

(4 citation statements)

References 145 publications

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“…Ocular involvement has been reported in 60% of CDG with a pure O-glycosylation defect (Francisco et al, 2018). G516R mutated patients also have ocular phenotypes, which are well aligned with our findings revealing O-glycosylation defects.…”

Section: Discussionsupporting

confidence: 91%

Development and Initial Characterization of Cellular Models for COG Complex-Related CDG-II Diseases

2021

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Conserved Oligomeric Golgi (COG) is an octameric protein complex that orchestrates intra-Golgi trafficking of glycosylation enzymes. Over a hundred individuals with 31 different COG mutations have been identified until now. The cellular phenotypes and clinical presentations of COG-CDGs are heterogeneous, and patients primarily represent neurological, skeletal, and hepatic abnormalities. The establishment of a cellular COG disease model will benefit the molecular study of the disease, explaining the detailed sequence of the interplay between the COG complex and the trafficking machinery. Moreover, patient fibroblasts are not a good representative of all the organ systems and cell types that are affected by COG mutations. We developed and characterized cellular models for human COG4 mutations, specifically in RPE1 and HEK293T cell lines. Using a combination of CRISPR/Cas9 and lentiviral transduction technologies, both myc-tagged wild-type and mutant (G516R and R729W) COG4 proteins were expressed under the endogenous COG4 promoter. Constructed isogenic cell lines were comprehensively characterized using biochemical, microscopy (superresolution and electron), and proteomics approaches. The analysis revealed similar stability and localization of COG complex subunits, wild-type cell growth, and normal Golgi morphology in all three cell lines. Importantly, COG4-G516R cells demonstrated increased HPA-647 binding to the plasma membrane glycoconjugates, while COG4-R729W cells revealed high GNL-647 binding, indicating specific defects in O- and N-glycosylation. Both mutant cell lines express an elevated level of heparin sulfate proteoglycans. Moreover, a quantitative mass-spectrometry analysis of proteins secreted by COG-deficient cell lines revealed abnormal secretion of SIL1 and ERGIC-53 proteins by COG4-G516R cells. Interestingly, the clinical phenotype of patients with congenital mutations in the SIL1 gene (Marinesco-Sjogren syndrome) overlaps with the phenotype of COG4-G516R patients (Saul-Wilson syndrome). Our work is the first compressive study involving the creation of different COG mutations in different cell lines other than the patient’s fibroblast. It may help to address the underlying cause of the phenotypic defects leading to the discovery of a proper treatment guideline for COG-CDGs.

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Section: Discussionsupporting

confidence: 91%

Development and Initial Characterization of Cellular Models for COG Complex-Related CDG-II Diseases

2021

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“…These are merely three groups of examples in which the power of the glycome is finally being harnessed for human health, but it potentially goes much deeper. The identification of congenital disorders of glycosylation is increasing [61], and novel approaches to target galectin molecules (mammalian lectins which associate with common glycan signatures on host cells) in anti-cancer therapies are ongoing and gaining a lot of attention [62]. And despite these exciting developments, there is much more to be discovered.…”

Section: Translational Glycomicsmentioning

confidence: 99%

The Glycoscience of Immunity

Zhou

Oswald

Oliva

et al. 2018

Trends in Immunology

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Carbohydrates, or glycans, are as integral to biology as nucleic acids and proteins. In immunology, glycans are well known to drive diverse functions ranging from glycosaminoglycan-mediated chemokine presentation and selectin-dependent leukocyte trafficking to the discrimination of self and non-self through the recognition of sialic acids by Siglec (sialic acid-binding Ig-like lectin) receptors. In recent years, a number of key immunological discoveries are driving a renewed and burgeoning appreciation for the importance of glycans. In this review, we highlight these findings which collectively help to define and refine our knowledge of the function and impact of glycans within the immune response.

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“…The majority of CDG patients present multisystem organ impairment with a vast clinical diversity ranging from mild to severe dysfunction (Monticelli et al 2016;Marques-da-Silva et al 2017a, b;Francisco et al 2018). Liver involvement in CDG also ranges from mild to severe.…”

Section: Congenital Disorders Of Glycosylationmentioning

confidence: 99%

An Electronic Questionnaire for Liver Assessment in Congenital Disorders of Glycosylation (LeQCDG): A Patient-Centered Study

Marques‐da‐Silva

Francisco

Ferreira³

et al. 2018

JIMD Reports

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Congenital disorders of glycosylation (CDG) are ultra-rare diseases showing a great phenotypic diversity ranging from mono- to multi-organ/multisystem involvement. Liver involvement, mostly nonprogressive, is often reported in CDG patients. The main objectives of this work were (1) to better understand liver involvement in CDG patients through a liver electronic questionnaire targeting CDG families (LeQCDG) and (2) to compare responses from LeQCDG participants with literature review regarding the prevalence of liver disease and the occurrence of liver symptoms in CDG patients. The network of patient advocacy groups, families and professionals (CDG & Allies - PPAIN) developed the LeQCDG by adapting validated published questionnaires. The LeQCDG was approved by an ethics committee, and the recruitment of patients and caregivers proceeded through social media platforms. Participants were asked to report past or present liver-related symptoms (e.g. hepatomegaly, liver fibrosis and cirrhosis) and laboratory results (e.g. biochemical and/or radiological). From 11 December 2016 to 22 January 2017, 155 questionnaires were completed. Liver disease was present in 29.9% of CDG patients. Main symptoms reported included hepatomegaly, increased levels of serum transaminases, fibrosis, steatosis and cirrhosis. The data obtained in this online survey confirm findings from a recent literature review of 25 years of published evidence (r = 0.927, P = 0.02). Our questionnaire collected large amounts of meaningful, clinical and patient-oriented data in a short period of time without geographic limitations. Internet-based approaches are especially relevant in the context of ultra-rare diseases such as CDG.

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Keeping an eye on congenital disorders of O-glycosylation: a systematic literature review

Cited by 7 publications

References 145 publications

Development and Initial Characterization of Cellular Models for COG Complex-Related CDG-II Diseases

Development and Initial Characterization of Cellular Models for COG Complex-Related CDG-II Diseases

The Glycoscience of Immunity

An Electronic Questionnaire for Liver Assessment in Congenital Disorders of Glycosylation (LeQCDG): A Patient-Centered Study

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