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Publications

February 2024

February 2, 2024

Instrumented assessment of gait disturbance in PMM2-CDG adults: a feasibility analysis

Cirnigliaro L, et al. , February 2, 2024

Congenital disorders of glycosylation (CDG) are genetic diseases caused by impaired synthesis of glycan moieties linked to glycoconjugates. Phosphomannomutase 2 deficiency (PMM2-CDG), the most frequent CDG, is characterized by prominent neurological involvement. Gait disturbance is a major cause of functional disability in patients with PMM2-CDG. However, no specific gait assessment for PMM2-CDG is available. This study analyses gait-related parameters in PMM2-CDG patients using a standardized clinical assessment and instrumented gait analysis (IGA).

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January 2024

January 27, 2024

Split but merge: Golgi fragmentation in physiological and pathological conditions

Zobaroğlu-Özer P, Bora-Akoğlu G. Mol Biol Rep, January 27, 2024

The Golgi complex is a highly dynamic and tightly regulated cellular organelle with essential roles in the processing as well as the sorting of proteins and lipids. Its structure undergoes rapid disassembly and reassembly during normal physiological processes, including cell division, migration, polarization, differentiation, and cell death. Golgi dispersal or fragmentation also occurs in pathological conditions, such as neurodegenerative diseases, infectious diseases, congenital disorders of glycosylation diseases, and cancer. In this review, current knowledge about both structural organization and morphological alterations in the Golgi in physiological and pathological conditions is summarized together with the methodologies that help to reveal its structure.

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January 22, 2024

Single-center experience of congenital disorders of glycosylation syndrome screening in Tunisia: A retrospective study over a 15-year period (2007-2021)

Zidi W, et al. Arch Pediatr., January 22, 2024

We report the results gathered over 15 years of screening for congenital disorders of glycosylation syndrome (CDGS) in Tunisia according to clinical and biochemical characteristics. Our laboratory received 1055 analysis requests from various departments and hospitals, for children with a clinical suspicion of CDGS. [...] During the 15-year period, 23 patients were diagnosed with CDGS (19 patients with CDG-Ia, three patients with CDG-IIx, and one patient with CDG-X).

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January 22, 2024

Proteomic screens of SEL1L-HRD1 ER-associated degradation substrates reveal its role in glycosylphosphatidylinositol-anchored protein biogenesis

Wei X, et al. Nat Commun., January 22, 2024

Endoplasmic reticulum-associated degradation (ERAD) plays indispensable roles in many physiological processes; however, the nature of endogenous substrates remains largely elusive. Here we report a proteomics strategy based on the intrinsic property of the SEL1L-HRD1 ERAD complex to identify endogenous ERAD substrates both in vitro and in vivo. [...] SEL1L-HRD1 ERAD attenuates the biogenesis of GPI-anchored proteins by specifically targeting PIGK for proteasomal degradation. Lastly, several PIGK disease variants in inherited GPI deficiency disorders are also SEL1L-HRD1 ERAD substrates.

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January 19, 2024

Genetic counseling for congenital disorders of glycosylation (CDG)

Weixel T, Wolfe L, Macnamara EF. J Genet Couns, January 19, 2024

Congenital disorders of glycosylation (CDGs) are a genetically and clinically diverse group of disorders that arise as a result of defects within glycosylation synthetic pathways. CDGs are caused by pathogenic variants in many different genes in the glycosylation network. [...] Thus, the role of the genetic counselor is paramount in helping affected individuals and their families navigate these genetic counseling complexities. Case examples of common genetic counseling difficulties for CDGs are outlined, providing clinical applications of what CDG presentations, diagnostic processes, and common difficulties look like. Information on the nomenclature, incidence, prevalence, diagnostic testing, treatment, and management of CDGs are also discussed to provide a comprehensive summary of CDGs for genetic counselors, and subsequently to affected individuals and their families.

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January 18, 2024

Targeted Proteomics Reveals Quantitative Differences in Low-Abundance Glycosyltransferases of Patients with Congenital Disorders of Glycosylation

Sakson R, et al. Int J Mol Sci., January 18, 2024

Protein glycosylation is an essential post-translational modification in all domains of life. Its impairment in humans can result in severe diseases named congenital disorders of glycosylation (CDGs). Most of the glycosyltransferases (GTs) responsible for proper glycosylation are polytopic membrane proteins that represent challenging targets in proteomics. We established a multiple reaction monitoring (MRM) assay to comprehensively quantify GTs involved in the processes of N-glycosylation and O- and C-mannosylation in the endoplasmic reticulum.

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January 16, 2024

Case report: A founder UGDH variant associated with developmental epileptic encephalopathy in Saudi Arabia

Alaamery M et al. Front Genet., January 16, 2024

Congenital disorders of glycosylation (CDG) are a group of more than 100 rare genetic disorders characterized by impaired glycosylation of proteins and lipids. The clinical presentation of CDG varies tremendously, from single-organ to multi-organ involvement and from prenatal death to a normal adult phenotype. In this case study, we report a large consanguineous family with multiple children suffering from cerebral palsy, seizure, developmental and epileptic encephalopathy, and global developmental delay. Whole-exome sequencing (WES) analysis revealed a homozygous variant in the UDP-glucose dehydrogenase (UGDH) gene (c.950G>A; p.R317Q) which segregates with the familial phenotype with a plausible autosomal recessive mode of inheritance, indicating a potential disease-causing association.

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January 13, 2024

Inherited Retinal Degeneration Caused by Dehydrodolichyl Diphosphate Synthase Mutation-Effect of an ALG6 Modifier Variant

Monson E, et al. Int J Mol Sci, January 13, 2024

Modern advances in disease genetics have uncovered numerous modifier genes that play a role in the severity of disease expression. One such class of genetic conditions is known as inherited retinal degenerations (IRDs), a collection of retinal degenerative disorders caused by mutations in over 300 genes. A single missense mutation (K42E) in the gene encoding the enzyme dehydrodolichyl diphosphate synthase (DHDDS), which is required for protein N-glycosylation in all cells and tissues, causes DHDDS-IRD (retinitis pigmentosa type 59 (RP59; OMIM #613861)). Apart from a retinal phenotype, however, DHDDS-IRD is surprisingly non-syndromic (i.e., without any systemic manifestations). To explore disease pathology, we selected five glycosylation-related genes for analysis that are suggested to have disease modifier variants. These genes encode glycosyltransferases (ALG6, ALG8), an ER resident protein (DDOST), a high-mannose oligosaccharyl transferase (MPDU1), and a protein N-glycosylation regulatory protein (TNKS).

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January 4, 2024

Molecules, metabolism and genetics

Morava E. Mol Genet Metab., January 4, 2024

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December 2023

December 29, 2023

A commentary on “Patient-derived gene and protein expression signatures of NGLY1 deficiency”

Suzuki T. J Biochem., December 29, 2023

The cytosolic peptide:N-glycanase (PNGase; NGLY1 in human and PNG1 in budding yeast) is a deglycosylating enzyme widely conserved in eukaryotes. Initially, functional importance of this enzyme remained unknown as the png1Δ mutant in yeast did not exhibit any significant phenotypes. However, the discovery of NGLY1 deficiency, a rare genetic disorder with biallelic mutations in NGLY1 gene, prompted an intensification of research that has resulted in uncovering the significance of NGLY1 as well as the proteins under its influence that are involved in numerous cellular processes. A recent report by Rauscher et al. (Patient-derived gene and protein expression signatures of NGLY1 deficiency. J. Biochem. 2022; 171: 187-199) presented a comprehensive summary of transcriptome/proteome analyses of various cell types derived from NGLY1 deficient patients. The authors also provide a web application called "NGLY1 browser", which will allow researchers to have access to a wealth of information on gene and protein expression signature for patients with NGLY1 deficiency.

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