Genetic Heterogeneity and Clinical Variability in Musculocontractural Ehlers-Danlos Syndrome Caused by Impaired Dermatan Sulfate Biosynthesis

2015 ◽  
Vol 36 (5) ◽  
pp. 535-547 ◽  
Author(s):  
Delfien Syx ◽  
Tim Van Damme ◽  
Sofie Symoens ◽  
Merel C. Maiburg ◽  
Ingrid van de Laar ◽  
...  
Keyword(s):  
Genetic Heterogeneity ◽  
Dermatan Sulfate ◽  
Ehlers Danlos Syndrome ◽  
Clinical Variability ◽  
Danlos Syndrome

scholarly journals Delineation of musculocontractural Ehlers–Danlos Syndrome caused by dermatan sulfate epimerase deficiency

2020 ◽  
Vol 8 (5) ◽  
Author(s):  
Charlotte K. Lautrup ◽  
Keng W. Teik ◽  
Ai Unzaki ◽  
Shuji Mizumoto ◽  
Delfien Syx ◽  
...  
Keyword(s):  
Dermatan Sulfate ◽  
Ehlers Danlos Syndrome ◽  
Danlos Syndrome

scholarly journals Vascular Ehlers–Danlos Syndrome in siblings with biallelic COL3A1 sequence variants and marked clinical variability in the extended family

2014 ◽  
Vol 23 (6) ◽  
pp. 796-802 ◽  
Author(s):  
Agnete Jørgensen ◽  
Toril Fagerheim ◽  
Svend Rand-Hendriksen ◽  
Per I Lunde ◽  
Torgrim O Vorren ◽  
...  
Keyword(s):  
Extended Family ◽  
Sequence Variants ◽  
Ehlers Danlos Syndrome ◽  
Clinical Variability ◽  
Danlos Syndrome

scholarly journals Gene Defect of Dermatan Sulfate Proteoglycan of Cattle Affected With a Variant Form of Ehlers-Danlos Syndrome

1999 ◽  
Vol 13 (3) ◽  
pp. 202-205 ◽  
Author(s):  
Motoshi Tajima ◽  
Sachiko Miyake ◽  
Kazushige Takehana ◽  
Ataru Kobayashi ◽  
Osamu Yamato ◽  
...  
Keyword(s):  
Dermatan Sulfate ◽  
Variant Form ◽  
Sulfate Proteoglycan ◽  
Gene Defect ◽  
Ehlers Danlos Syndrome ◽  
Dermatan Sulfate Proteoglycan ◽  
Danlos Syndrome

scholarly journals Defect in dermatan sulfate in urine of patients with Ehlers-Danlos syndrome caused by a CHST14/D4ST1 deficiency

2017 ◽  
Vol 50 (12) ◽  
pp. 670-677 ◽  
Author(s):  
Shuji Mizumoto ◽  
Tomoki Kosho ◽  
Atsushi Hatamochi ◽  
Tomoko Honda ◽  
Tomomi Yamaguchi ◽  
...  
Keyword(s):  
Dermatan Sulfate ◽  
Ehlers Danlos Syndrome ◽  
Danlos Syndrome

Systematic investigation of the skin in Chst14−/− mice: A model for skin fragility in musculocontractural Ehlers–Danlos syndrome caused by CHST14 variants (mcEDS-CHST14)

Glycobiology ◽  
2020 ◽  
Author(s):  
Takuya Hirose ◽  
Shuji Mizumoto ◽  
Ayana Hashimoto ◽  
Yuki Takahashi ◽  
Takahiro Yoshizawa ◽  
...  
Keyword(s):  
Chondroitin Sulfate ◽  
Anion Exchange ◽  
Dermatan Sulfate ◽  
Systematic Investigation ◽  
Exchange Chromatography ◽  
Collagen Fibrils ◽  
Loss Of Function ◽  
Ehlers Danlos Syndrome ◽  
Skin Fragility ◽  
Danlos Syndrome

Abstract Loss-of-function variants in CHST14 cause a dermatan 4-O-sulfotransferase deficiency named musculocontractural Ehlers–Danlos syndrome-CHST14 (mcEDS-CHST14), resulting in complete depletion of the dermatan sulfate moiety of decorin glycosaminoglycan (GAG) chains, which is replaced by chondroitin sulfate. Recently, we uncovered structural alteration of GAG chains in the skin of patients with mcEDS-CHST14. Here, we conducted the first systematic investigation of Chst14 gene-deleted homozygote (Chst14−/−) mice. We used skin samples of wild-type (Chst14+/+) and Chst14−/− mice. Mechanical fragility of the skin was measured with a tensile test. Pathology was observed using light microscopy, decorin immunohistochemistry and electron microscopy (EM) including cupromeronic blue (CB) staining. Quantification of chondroitin sulfate and dermatan sulfate was performed using enzymatic digestion followed by anion-exchange HPLC. In Chst14−/− mice, skin tensile strength was significantly decreased compared with that in Chst14+/+ mice. EM showed that collagen fibrils were oriented in various directions to form disorganized collagen fibers in the reticular layer. Through EM-based CB staining, rod-shaped linear GAG chains were found to be attached at one end to collagen fibrils and protruded outside of the fibrils, in contrast to them being round and wrapping the collagen fibrils in Chst14+/+ mice. A very low level of dermatan sulfate disaccharides was detected in the skin of Chst14−/− mice by anion-exchange chromatography. Chst14−/− mice, exhibiting similar abnormalities in the GAG structure of decorin and collagen networks in the skin, could be a reasonable model for skin fragility of patients with mcEDS-CHST14, shedding light on the role of dermatan sulfate in maintaining skin strength.

scholarly journals Musculocontractural Ehlers–Danlos syndrome and neurocristopathies: dermatan sulfate is required forXenopusneural crest cells to migrate and adhere to fibronectin

2016 ◽  
Vol 9 (6) ◽  
pp. 607-620 ◽  
Author(s):  
Nadège Gouignard ◽  
Marco Maccarana ◽  
Ina Strate ◽  
Kristoffer von Stedingk ◽  
Anders Malmström ◽  
...  
Keyword(s):  
Dermatan Sulfate ◽  
Ehlers Danlos Syndrome ◽  
Danlos Syndrome

scholarly journals Loss of dermatan sulfate epimerase (DSE) function results in musculocontractural Ehlers–Danlos syndrome

2013 ◽  
Vol 22 (18) ◽  
pp. 3761-3772 ◽  
Author(s):  
Thomas Müller ◽  
Shuji Mizumoto ◽  
Indrajit Suresh ◽  
Yoshie Komatsu ◽  
Julia Vodopiutz ◽  
...  
Keyword(s):  
Dermatan Sulfate ◽  
Ehlers Danlos Syndrome ◽  
Danlos Syndrome

scholarly journals Congenital Disorders of Deficiency in Glycosaminoglycan Biosynthesis

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuji Mizumoto ◽  
Shuhei Yamada
Keyword(s):  
Extracellular Matrix ◽  
Dermatan Sulfate ◽  
Congenital Disorders ◽  
Connective Tissue Disorders ◽  
Ehlers Danlos Syndrome ◽  
Core Proteins ◽  
Multiple Exostoses ◽  
Extracellular Matrix Components ◽  
Immune Deficiencies ◽  
Danlos Syndrome

Glycosaminoglycans (GAGs) including chondroitin sulfate, dermatan sulfate, and heparan sulfate are covalently attached to specific core proteins to form proteoglycans, which are distributed at the cell surface as well as in the extracellular matrix. Proteoglycans and GAGs have been demonstrated to exhibit a variety of physiological functions such as construction of the extracellular matrix, tissue development, and cell signaling through interactions with extracellular matrix components, morphogens, cytokines, and growth factors. Not only connective tissue disorders including skeletal dysplasia, chondrodysplasia, multiple exostoses, and Ehlers-Danlos syndrome, but also heart and kidney defects, immune deficiencies, and neurological abnormalities have been shown to be caused by defects in GAGs as well as core proteins of proteoglycans. These findings indicate that GAGs and proteoglycans are essential for human development in major organs. The glycobiological aspects of congenital disorders caused by defects in GAG-biosynthetic enzymes including specific glysocyltransferases, epimerases, and sulfotransferases, in addition to core proteins of proteoglycans will be comprehensively discussed based on the literature to date.

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