DDOST Mutations Identified by Whole-Exome Sequencing Are Implicated in Congenital Disorders of Glycosylation

Jones, Melanie A.; Ng, Bobby G.; Bhide, Shruti; Chin, Ephrem; Rhodenizer, Devin; He, Ping; Losfeld, Marie-Estelle; He, Miao; Raymond, Kimiyo; Berry, Gerard T.; Freeze, Hudson H.; Hegde, Madhuri

doi:10.1016/j.ajhg.2011.12.024

Cited by 62 publications

(65 citation statements)

References 25 publications

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“…This is likely attributable to impaired N-glycosylation. Indeed, there is only one report of a living family with a mutation in DDOST where the children had a loss of function mutation leading to a congenital disorder of glycosylation [57]. This loss of function mutation in DDOST, did not present with clinically obvious diabetes or kidney disease, however, this is likely because individuals with mutations in genes involved in glycosylation generally do not survive past childhood due to systemic organ dysfunction [57,58].…”

Section: The Mechanistic Pathways Of Age-r1mentioning

confidence: 96%

Diabetic kidney disease: a role for advanced glycation end-product receptor 1 (AGE-R1)?

Zhuang

Forbes

2016

Glycoconj J

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Diabetic patients are postulated to be in a perpetual state of oxidative stress and inflammation at sites where chronic complications occur. The accumulation of AGEs derived from both endogenous and exogenous sources (such as the diet) have been implicated in the development and progression of diabetic complications, particularly nephropathy. There has been some interest in investigating the potential for reducing the AGE burden in chronic disease, through the action of AGE "clearance" receptors, such as the advanced glycation end-product receptor 1 (AGE-R1). Reducing the burden of AGEs has been linked to attenuation of inflammation, slower progression of diabetic complications (in particular vascular and renal complications) and has been shown to extend lifespan. To date, however, there have been no direct investigations into whether AGE-R1 has any role in modulating normal kidney function, or specifically during the development and progression of diabetes. This mini-review will focus on the recent advances in knowledge around the mechanistic function of AGE-R1 and the implications of this for the pathogenesis of diabetic kidney disease.

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Section: The Mechanistic Pathways Of Age-r1mentioning

confidence: 96%

Diabetic kidney disease: a role for advanced glycation end-product receptor 1 (AGE-R1)?

Zhuang

Forbes

2016

Glycoconj J

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“…and Western blotting were carried out as described by Jones et al (9). For detection of ICAM-1 in human fibroblasts, ECL substrate with higher sensitivity (WesternBright Quantum) or an Immun-Star WesternC kit was used.…”

Section: Sds-page and Western Blotting-sds-pagementioning

confidence: 99%

“…Gene Complementation-The PMM2 (phosphomannomutase-2) complementation was done as described by Jones et al (9), except that PMM2 was tagged with FLAG (DYKDDDDK) at the N terminus.…”

Section: Sds-page and Western Blotting-sds-pagementioning

confidence: 99%

Identification of Intercellular Cell Adhesion Molecule 1 (ICAM-1) as a Hypoglycosylation Marker in Congenital Disorders of Glycosylation Cells

He¹,

Ng²,

Losfeld³

et al. 2012

Journal of Biological Chemistry

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“…Likewise, fibroblasts from CDG patients with a mutation in the DDOST gene, which encodes OST48, have a general defect in Nlinked glycosylation (Jones et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Glycosylation of closely spaced acceptor sites in human glycoproteins

Shrimal

Gilmore

2013

Journal of Cell Science

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SummaryAsparagine-linked glycosylation of proteins by the oligosaccharyltransferase (OST) occurs when acceptor sites or sequons (N-x?P-T/S) on nascent polypeptides enter the lumen of the rough endoplasmic reticulum. Metazoan organisms assemble two isoforms of the OST that have different catalytic subunits (STT3A or STT3B) and partially non-overlapping cellular roles. Potential glycosylation sites move past the STT3A complex, which is associated with the translocation channel, at the protein synthesis elongation rate. Here, we investigated whether close spacing between acceptor sites in a nascent protein promotes site skipping by the STT3A complex. Biosynthetic analysis of four human glycoproteins revealed that closely spaced sites are efficiently glycosylated by an STT3B-independent process unless the sequons contain non-optimal sequence features, including extreme close spacing between sequons (e.g. NxTNxT) or the presence of paired NxS sequons (e.g. NxSANxS). Many, but not all, glycosylation sites that are skipped by the STT3A complex can be glycosylated by the STT3B complex. Analysis of a murine glycoprotein database revealed that closely spaced sequons are surprisingly common, and are enriched for paired NxT sites when the gap between sequons is less than three residues.

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DDOST Mutations Identified by Whole-Exome Sequencing Are Implicated in Congenital Disorders of Glycosylation

Cited by 62 publications

References 25 publications

Diabetic kidney disease: a role for advanced glycation end-product receptor 1 (AGE-R1)?

Diabetic kidney disease: a role for advanced glycation end-product receptor 1 (AGE-R1)?

Identification of Intercellular Cell Adhesion Molecule 1 (ICAM-1) as a Hypoglycosylation Marker in Congenital Disorders of Glycosylation Cells

Glycosylation of closely spaced acceptor sites in human glycoproteins

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