Defective glycosylation of decorin and biglycan, altered collagen structure, and abnormal phenotype of the skin fibroblasts of an Ehlers–Danlos syndrome patient carrying the novel Arg270Cys substitution in galactosyltransferase I (β4GalT-7)

@article{Seidler2006DefectiveGO,
  title={Defective glycosylation of decorin and biglycan, altered collagen structure, and abnormal phenotype of the skin fibroblasts of an Ehlers–Danlos syndrome patient carrying the novel Arg270Cys substitution in galactosyltransferase I ($\beta$4GalT-7)},
  author={Daniela G. Seidler and Muhammad Faiyaz-ul-Haque and Uwe Hansen and George W. Yip and Syed Hassan Ejaz Zaidi and Ahmad Said Teebi and Ludwig Kiesel and Martin G{\"o}tte},
  journal={Journal of Molecular Medicine},
  year={2006},
  volume={84},
  pages={583-594}
}
The Ehlers–Danlos syndrome (EDS) is a heterogeneous group of connective tissue disorders affecting skin and joint function. Molecular defects in extracellular matrix proteins, including collagen (type I, III, and V) and tenascin X are associated with different forms of EDS. Compound heterozygous mutations in the B4GALT7 gene, resulting in aberrant glycosylation of the dermatan sulfate proteoglycan decorin, had been described in a single patient affected with the progeroid form of EDS. We have… Expand
Glycan profiling of a defect in decorin glycosylation in equine systemic proteoglycan accumulation, a potential model of progeroid form of Ehlers-Danlos syndrome.
TLDR
Using liquid chromatography/mass spectrometry, and one- and two-dimensional immunoblotting, it is determined that decorin from ESPA-tendons had a higher molecular weight than decor in from non-affected control tendons. Expand
The glycosaminoglycan chain of decorin plays an important role in collagen fibril formation at the early stages of fibrillogenesis
TLDR
Data show that at early stages of fibrillogenesis, the glycosaminoglycan chain of decorin has a reducing effect on collagen fibril diameter, with the latter showing the most prominent effects. Expand
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TLDR
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A decorin-deficient matrix affects skin chondroitin/dermatan sulfate levels and keratinocyte function.
TLDR
The results provide novel mechanistic explanations for the reported defects in wound healing in Dcn(-/-) mice and possibly Ehlers-Danlos patients and an altered CS/DS composition differentially influence keratinocyte behavior. Expand
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TLDR
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TLDR
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TLDR
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TLDR
The phenotype of B4GALT7-related linkeropathies is expanded to include lethal skeletal dysplasia due to more severe loss of function, and the p.(Gln133Arg) had almost no enzyme activity and little production of heparan sulfate GAGs, while p.(Arg270Cys) only had 17% of wild-type activity. Expand
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References

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TLDR
The ß4galT-7 mutations directly affect the molecular phenotype of decorin observed in a patient with the progeroid form of Ehlers-Danlos syndrome, which may be a major mechanistic cause for the skin and wound healing defects observed in this patient. Expand
A genetic defect in the biosynthesis of dermatan sulfate proteoglycan: galactosyltransferase I deficiency in fibroblasts from a patient with a progeroid syndrome.
TLDR
Fibroblasts from a patient with progeroidal appearance and symptoms of the Ehlers-Danlos syndrome have a reduced ability of converting the core protein of this proteoglycan into a mature glycosaminoglycan chain-bearing species. Expand
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TLDR
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TLDR
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TLDR
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TLDR
3 patients with mixed phenotypes of EDS, who have significantly decreased mRNAs for LH2, but normal levels of LH1 and LH3 m RNAs, in their skin fibroblasts are described, suggesting that the deficiency of LH2 in these fibro Blasts may be caused by changes in other factors required for the expression of LH 2. Expand
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TLDR
Though these results do not define the basic defect unambiguously, they provide the first report of a disorder being due to an abnormality in small proteoglycan biosynthesis. Expand
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TLDR
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TLDR
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TLDR
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