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Publications

August 2022

August 10, 2022

In special coagulation, think horses not zebras: A clotted sample from a patient with congenital disorder of glycosylation

Saadalla A, Stuart M, Ashrani A, Pruthi R, Morava E, Chen D, Seheult J. Int J Lab Hematol., August 10, 2022

Herein, we describe an interesting case of non-parallelism in coagulation factor activity assays observed in a sample collected from a 4-year-old patient with a congenital disorder of glycosylation (CDG), and emphasise the importance of rigorously assessing for pre-analytical variables when interpreting atypical patterns in coagulation factor activity testing.

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August 8, 2022

Missense variant c.1460 T > C (p.L487P) enhances protein degradation of ER mannosyltransferase ALG9 in two new ALG9-CDG patients presenting with West syndrome and review of the literature

Himmelreich N. et al. Mol Genet Metab. , August 8, 2022

ALG9-CDG is a CDG-I defect within the group of Congenital Disorders of Glycosylation (CDG). We here describe the clinical symptoms of two new and unrelated ALG9-CDG patients, both carrying the novel homozygous missense variant c.1460 T > C (p.L487P) in the ALG9 gene which led to global developmental delay, psychomotor disability, facial dysmorphisms, brain and heart defects, hearing loss, hypotonia, as well as feeding problems. New clinical symptoms comprised West syndrome with hypsarrhythmia. [...] The clinical findings of our patients and of all previously published ALG9-CDG patients are brought together to further expand the knowledge about this rare N-glycosylation disorder. 

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August 8, 2022

Lab-in-droplet: From glycan sample treatment toward diagnostic screening of congenital disorders of glycosylation.

Liénard-Mayor T, Bricteux C, Bendali A, Tran NT, Bruneel A, Taverna M, Mai TD. Anal Chim Acta., August 8, 2022

chieved through several features that are not met in previous droplet setups, notably full automation, droplet sensing and heating. [...] We demonstrated the superiority of this Lab-in-Droplet over the conventional batchwise protocol, with 10-fold less reagent consumption, 3-fold less time, and 2-fold improvement of glycan labeling yield, without degradation of glycan separation profile obtained by capillary electrophoresis. The platform with the developed droplet protocol was applied successfully for mapping N-linked glycans released from human sera, serving for diagnostic screening of congenital disorders of glycosylation.

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August 6, 2022

A recurrent homozygous missense DPM3 variant leads to muscle and brain disease.

Nagy S. et al. Clinic Genet., August 6, 2022

PM) which produce mannosyl donors for glycosylphosphatidylinositols, N-glycan and protein O- and C-mannosylation, are rare causes of congenital disorders of glycosylation. Pathogenic variants in DPM1 and DPM2 are associated with muscle-eye-brain (MEB) disease, whereas DPM3 variants have mostly been reported in patients with isolated muscle disease- dystroglycanopathy. [...]Here we present five affected individuals from four unrelated families with global developmental delay/intellectual disability ranging from mild to severe, microcephaly, seizures, WMA, muscle weakness and variable cardiomyopathy.

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August 5, 2022

Systematic Review: Drug Repositioning for Congenital Disorders of Glycosylation (CDG)

Brasil S, et al. Int J Mol Sci. , August 5, 2022

Advances in research have boosted therapy development for congenital disorders of glycosylation (CDG), a group of rare genetic disorders affecting protein and lipid glycosylation and glycosylphosphatidylinositol anchor biosynthesis. The (re)use of known drugs for novel medical purposes, known as drug repositioning, is growing for both common and rare disorders. The latest innovation concerns the rational search for repositioned molecules which also benefits from artificial intelligence (AI). [...] This work reviews the literature related to repositioned drugs for CDG, discovered by serendipity or through a systemic approach. Recent advances in biomarkers and disease models are also outlined as well as stakeholders' views on AI for therapy discovery in CDG.

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July 2022

July 30, 2022

Stakeholders’ views on drug development: the congenital disorders of glycosylation community perspective

Monticelli M, Francisco R, Brasil S et al. Orphanet J Rare Dis., July 30, 2022

Congenital disorders of glycosylation (CDG) are a large family of rare genetic diseases for which therapies are virtually nonexistent. However, CDG therapeutic research has been expanding, thanks to the continuous efforts of the CDG medical/scientific and patient communities. Hence, CDG drug development is a popular research topic. The main aim of this study was to understand current and steer future CDG drug development and approval by collecting and analysing the views and experiences of the CDG community, encompassing professionals and families.

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July 27, 2022

A case of ALG11-congenital disorders of glycosylation diagnosed by post-mortem whole exome sequencing

Arai Y, Okanishi T, Kanai S et al. Brain Dev., July 27, 2022

CDG poses a serious diagnostic challenge; therefore, whole-exome sequencing (WES), which plays an increasingly important role in the molecular diagnosis of CDG, is used for examining patients with CDG. [...] We present a case of the patient with ALG11-CDG diagnosed using post-mortem WES. The EEG revealed a S-B pattern that indicated severely drug-resistant DEE, which was associated with poor prognosis. If a CDG is suspected, WES should be considered.

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July 23, 2022

SLC35A2 Deficiency Promotes an Epithelial-to-Mesenchymal Transition-like Phenotype in Madin-Darby Canine Kidney Cells

Kot M, Mazurkiewicz E, Wiktor M et al. Cells., July 23, 2022

In mammalian cells, SLC35A2 delivers UDP-galactose for galactosylation reactions that take place predominantly in the Golgi lumen. Mutations in the corresponding gene cause a subtype of a congenital disorder of glycosylation (SLC35A2-CDG). Although more and more patients are diagnosed with SLC35A2-CDG, the link between defective galactosylation and disease symptoms is not fully understood. According to a number of reports, impaired glycosylation may trigger the process of epithelial-to-mesenchymal transition (EMT). We therefore examined whether the loss of SLC35A2 activity would promote EMT in a non-malignant epithelial cell line.

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July 18, 2022

Bioinformatic prediction of putative conveyers of O-GlcNAc Transferase intellectual disability

Mitchell CW, Czajewski I, van Aalten DMF. J Biol Chem., July 18, 2022

ology of OGT-CDG is that loss of OGT activity leads to hypo-O-GlcNAcylation of as yet unidentified, specific neuronal proteins, affecting essential embryonic and postnatal neurodevelopmental processes; however, the identity of these O-GlcNAcylated proteins is not known. Here, we used bioinformatic techniques to integrate sequence conservation, structural data, clinical data, and the available literature to identify 22 candidate proteins that convey OGT-CDG. 

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July 13, 2022

Case Report: DPM1-CDG: Novel Variant with Severe Phenotype and Literature Review

Lausmann H, Zacharias M, Neuhann TM, Locher MK, Schettler KF. Front Genet., July 13, 2022

electroencephalography abnormalities and dysmorphic features with varying disease onset and severity. [...] The presented case extends the spectrum of DPM1-CDG to a very young and severely affected child. The deletion of Lys80 in DPM1 results in an impaired helical configuration. This has implications for further understanding the association of structure and function of DPM1.

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