Carbohydrate-deficient glycoprotein syndromes: Peculiar group of new disorders

Hagberg, B; Blennow, Gösta; Kristiansson, Bengt; Stibler, Helena

doi:10.1016/0887-8994(93)90060-p

Cited by 134 publications

(82 citation statements)

References 24 publications

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“…Abbreviations used in this paper: CDGS, Carbohydrate-deficient Glycoprotein Syndrome; Con A, concanavalin A; Dol, dolichol; ER, endoplasmic reticulum; Gal, galactose; GalNAc, N-acetyl-galactosamine; GlcNAc, N-acetyl-glucosamine; HPAE, HPLC anion exchange chromatography with pulsed amperometric detection; LLO, lipid-linked oligosaccharide; Man, mannose; PNGase F, peptide-N4-(N-acetyl-13-glucosaminyl)asparigine amidase; Sia, sialic acid; TBA, thiobarbituric acid assay; TFA, trifluoroacetic acid. der affecting multiple organ systems including the central and peripheral nervous systems, liver, bone, adipose tissue, and genital organs (1)(2)(3)(4)(5)(6)(7)(8)(9). Within the first few months of life, affected children present with neurological abnormalities, and their development is marked by variable but often severe psychomotor retardation, lower motor neuron dysfunction, abnormal facies, skeletal anomalies, variable hepatomegaly, and other clinical symptoms and signs.…”

Section: Introductionmentioning

confidence: 99%

Carbohydrate-deficient glycoprotein syndrome: not an N-linked oligosaccharide processing defect, but an abnormality in lipid-linked oligosaccharide biosynthesis?

Powell¹,

Paneerselvam²,

Vij³

et al. 1994

J. Clin. Invest.

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The carbohydrate-deficient glycoprotein syndrome (CDGS) is a developmental disease associated with an abnormally high isoelectric point of serum transferrin. Carbohydrate analyses of this glycoprotein initially suggested a defect in N-linked oligosaccharide processing, although more recent studies indicate a defect in the attachment of these sugar chains to the protein. We studied both serum glycoproteins and fibroblast-derived [2-3H]mannose-labeled oligosaccharides from CDGS patients and normal controls. While there was a decrease in the glycosylation of serum glycoproteins of affected individuals, differences were not seen in either monosaccharide composition or oligosaccharide structures. The lectin-binding profiles of glycopeptides from [2-3H]-mannose-labeled fibroblasts were likewise indistinguishable. However, the incorporation of [2-3H]mannose into both glycoproteins and the dolichol-linked oligosaccharide precursor was significantly reduced. Thus, at least in some patients, CDGS is not due to a defect in processing of N-linked oligosaccharides, but rather to defective synthesis and transfer of nascent dolichol-linked oligosaccharide precursors. This abnormality could result in both a failure to glycosylate some sites on some proteins, as well as secondary abnormalities in overall glycoprotein processing and/or function. (J.

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Section: Introductionmentioning

confidence: 99%

Carbohydrate-deficient glycoprotein syndrome: not an N-linked oligosaccharide processing defect, but an abnormality in lipid-linked oligosaccharide biosynthesis?

Powell¹,

Paneerselvam²,

Vij³

et al. 1994

J. Clin. Invest.

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“…1,2 Biochemical diagnosis relies on isoelectric focusing of serum glycoproteins which shows a cathodal shift of isoforms due to undersialylation. 3 The majority of CDG1 patients have a deficiency of phosphomannomutase which converts mannose-6-P to mannose-1-P. [4][5][6] A locus for CDG1 has been mapped to 16p13, [7][8][9] and overrepresentation of a certain haplotype in CDG1 families from southern Scandinavia suggests the presence of a specific mutation with a founder effect in this area.…”

Section: Introductionmentioning

confidence: 99%

Absence of homozygosity for predominant mutations in PMM2 in Danish patients with carbohydrate-deficient glycoprotein syndrome type 1

1998

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Carbohydrate-deficient glycoprotein syndrome type 1 (CDG1; McKusick No. 212065) is an autosomal recessively inherited disease characterised clinically by central nervous system dysfunction and biochemically by hypoglycosylation of many serum proteins. Most patients with CDG1 have deficient activity of phosphomannomutase. The locus for this enzyme has been mapped to 16p13, and a gene, PMM2, encoding phosphomannomutase has been isolated. We identified 34 mutations on 36 disease chromosomes in 18 unrelated Danish patients with CDG1. All patients have less than 15% residual activity of phosphomannomutase. Two mutations account for 88% of all mutations: F119L and R141H were each found in 16 out of 36 CDG1 alleles. These two mutations were found to be in linkage disequilibrium with two different alleles of the marker D16S3020, suggesting that there is one ancestral origin for each mutation. Two new mutations, G117R and D223E, were identified also. Surprisingly, no patient was homozygous for either of the two common mutations, suggesting that homozygosity for these mutations is either lethal or so benign that such patients are not detected.

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“…IEF of plasma sialotransferrin (TfIEF) shows an increase of the non-and poorly sialylated cathodal fractions and a decrease of the more anodal, normally sialylated Tfs. In a large portion of serum Tfs up to two of the normal four N-linked trisaccharides are absent (9,10,17,18). CDG-Ia shares this TfIEF profile with the other CDGs due to defects in the assembly stage of N-glycosylation, which identified them as CDG-I entities (9).…”

Section: Leroymentioning

confidence: 99%

“…Inverted and laterally displaced nipples are less consistent features. In some patients the distribution of s.c. fat is abnormal over the buttocks and suprapubic region and lipodystrophic skin changes may develop in the pelvic region and over the thighs (10,12). However, in many patients abnormal physical features are absent.…”

Section: The Type I Congenital Disorders Of N-glycosylation (Cdg-i)mentioning

confidence: 99%

Congenital Disorders of N-Glycosylation Including Diseases Associated With O- as Well as N-Glycosylation Defects

Leroy

2006

Pediatr Res

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Carbohydrate-deficient glycoprotein syndromes: Peculiar group of new disorders

Cited by 134 publications

References 24 publications

Carbohydrate-deficient glycoprotein syndrome: not an N-linked oligosaccharide processing defect, but an abnormality in lipid-linked oligosaccharide biosynthesis?

Carbohydrate-deficient glycoprotein syndrome: not an N-linked oligosaccharide processing defect, but an abnormality in lipid-linked oligosaccharide biosynthesis?

Absence of homozygosity for predominant mutations in PMM2 in Danish patients with carbohydrate-deficient glycoprotein syndrome type 1

Congenital Disorders of N-Glycosylation Including Diseases Associated With O- as Well as N-Glycosylation Defects

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