Congenital Disorders of Glycosylation with Emphasis on Cerebellar Involvement

Barone, Rita; Fiumara, Agata; Jaeken, Jaak

doi:10.1055/s-0034-1387197

Cited by 66 publications

(71 citation statements)

References 76 publications

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“…A common feature of PMM2-CDG children is cerebellar atrophy/hypoplasia (Barone et al 2014). Autopsy studies show extensive loss of Purkinje and granule cells (CGC) (Aronica et al 2005).…”

Section: Biosynthetic Pathways and Consequences Of Their Disruptionmentioning

confidence: 99%

Neurological Aspects of Human Glycosylation Disorders

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Eklund²,

et al. 2015

Annu. Rev. Neurosci.

202

170

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This review will present principles of glycosylation, describe the relevant glycosylation pathways and their related disorders, and highlight some of the neurological aspects and issues that continue to challenge researchers. Over 100 rare human genetic disorders that result from deficiencies in the different glycosylation pathways are known today. Most of these disorders impact the central and/or peripheral nervous systems. Patients typically have developmental delay/intellectual disability, hypotonia, seizures, neuropathy, and metabolic abnormalities in multiple organ systems. Between these disorders there is great clinical diversity because all cell types differentially glycosylate proteins and lipids. The patients have hundreds of mis-glycosylated products afflicting a myriad of processes including cell signaling, cell-cell interaction and cell migration. This vast complexity in glycan composition and function, along with limited analytic tools has impeded the identification of key glycosylated molecules that cause pathologies, and to date few critical target proteins have been pinpointed.

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“…A common feature of PMM2-CDG children is cerebellar atrophy/hypoplasia (Barone et al 2014). Autopsy studies show extensive loss of Purkinje and granule cells (CGC) (Aronica et al 2005).…”

Section: Biosynthetic Pathways and Consequences Of Their Disruptionmentioning

confidence: 99%

Neurological Aspects of Human Glycosylation Disorders

Freeze

Eklund²,

et al. 2015

Annu. Rev. Neurosci.

202

170

View full text Add to dashboard Cite

show abstract

“…Glycosylation represents an important post-translational modification of proteins in a vast number of different tissues. While congenital disorders of glycosylation have been shown to affect central nervous function [38], glycosylation has also been related to the development and progression of several different types of cancer and other diseases unrelated to the brain [39]. Interestingly, it has been shown that inbreeding in human populations strongly affects the glycosylation of human plasma proteins, potentially leading to the increased prevalence of tumors that has been reported in certain isolated populations as well as other phenotypic changes [40].…”

Section: Discussionmentioning

confidence: 99%

The Genetics of Asymmetry: Whole Exome Sequencing in a Consanguineous Turkish Family with an Overrepresentation of Left-Handedness

et al. 2017

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Abstract:Handedness is the most pronounced behavioral asymmetry in humans. Genome-wide association studies have largely failed to identify genetic loci associated with phenotypic variance in handedness, supporting the idea that the trait is determined by a multitude of small, possibly interacting genetic and non-genetic influences. However, these studies typically are not capable of detecting influences of rare mutations on handedness. Here, we used whole exome sequencing in a Turkish family with history of consanguinity and overrepresentation of left-handedness and performed quantitative trait analysis with handedness lateralization quotient as a phenotype. While rare variants on different loci showed significant association with the phenotype, none was functionally relevant for handedness. This finding was further confirmed by gene ontology group analysis. Taken together, our results add further evidence to the suggestion that there is no major gene or mutation that causes left-handedness.

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“…Patient 1 was included in a panel targeting 25 genes known to cause CDG-I +GALT/ALDOB. 4 Array-CGH (Agilent 180K platform; Agilent Technologies, Santa Clara, CA, USA) and targeted resequencing of a panel of 95 epilepsy-related genes was performed in three children (1)(2)(3). The genes targeted by this panel are listed in Table SI (online supporting information).…”

Section: Genetic Studiesmentioning

confidence: 99%

“…[1][2][3] Isoelectrofocusing of transferrin (TIEF) is the screening test for N-glycosylation defects, while isoelectrofocusing of apolipoprotein C-III is utilized to detect O-glycan synthesis disorders. Since their first description in 1980, several protein N-and O-glycosylation defects have been identified.…”

mentioning

confidence: 99%

“…[1][2][3] Isoelectrofocusing of transferrin (TIEF) is the screening test for N-glycosylation defects, while isoelectrofocusing of apolipoprotein C-III is utilized to detect O-glycan synthesis disorders. 1,2 As a consequence of their phenotypic variability, CDG represent a diagnostic challenge and are still largely under-diagnosed. 1,2 Confirmation of clinical and biochemical diagnosis of CDG-I relies on enzymatic studies in leukocytes or fibroblasts and lipid-linked oligosaccharide (LLO) analysis in fibroblasts, followed by molecular analysis to detect underlying gene defects.…”

mentioning

confidence: 99%

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