Loss of dermatan sulfate epimerase (DSE) function results in musculocontractural Ehlers-Danlos syndrome.
paper
Cited
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- Authors
- Müller, Thomas; Mizumoto, Shuji; Suresh, Indrajit; Komatsu, Yoshie; Vodopiutz, Julia; Dundar, Munis; Straub, Volker; Lingenhel, Arno; Melmer, Andreas; Lechner, Silvia; Zschocke, Johannes; Sugahara, Kazuyuki; Janecke, Andreas R
- Year
- 2013
- Journal
- Human molecular genetics
- PMID
- 23704329
- DOI
- 10.1093/hmg/ddt227
The sulfated polysaccharide dermatan sulfate (DS) forms proteoglycans with a number of distinct core proteins. Iduronic acid-containing domains in DS have a key role in mediating the functions of DS proteoglycans. Two tissue-specific DS epimerases, encoded by DSE and DSEL, and a GalNAc-4-O-sulfotransferase encoded by CHST14 are necessary for the formation of these domains. CHST14 mutations were previously identified for patients with the musculocontractural type of Ehlers-Danlos syndrome (MCEDS). We now identified a homozygous DSE missense mutation (c.803C>T, p.S268L) by the positional candidate approach in a male child with MCEDS, who was born to consanguineous parents. Heterologous expression of mutant full-length and soluble recombinant DSE proteins showed a loss of activity towards partially desulfated DS. Patient-derived fibroblasts also showed a significant reduction in epimerase activity. The amount of DS disaccharides was markedly decreased in the conditioned medium and the cell fraction from cultured fibroblasts of the patient when compared with a healthy control subject, whereas no apparent difference was observed in the chondroitin sulfate (CS) chains from the conditioned media. However, the total amount of CS disaccharides in the cell fraction from the patient was increased ∼1.5-fold, indicating an increased synthesis or a reduced conversion of CS chains in the cell fraction. Stable transfection of patient fibroblasts with a DSE expression vector increased the amount of secreted DS disaccharides. DSE deficiency represents a specific defect of DS biosynthesis. We demonstrate locus heterogeneity in MCEDS and provide evidence for the importance of DS in human development and extracellular matrix maintenance.
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| A genome wide association study of fast beta EEG in families of European ancestry. | 2017 | 28040410 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| CANT1 Is Involved in Collagen Fibrogenesis in Tendons by Regulating the Synthesis of Dermatan/Chondroitin Sulfate Attached to the Decorin Core Protein. | Yamashita R et al. | — | 2025 | → |
| Carbohydrate sulfotransferase 14 gene deletion induces dermatan sulfate deficiency and affects collagen structure and bowel contraction. | Ono F et al. | — | 2025 | → |
| Congenital disorders caused by aberrations in the biosynthesis of chondroitin/dermatan sulfate. | Mikami T et al. | — | 2025 | → |
| Dermatan Sulfate: Structure, Biosynthesis, and Biological Roles. | Chen C et al. | — | 2025 | → |
| The circular RNA expression profile of human auricle cartilage and the role of circCOL1A2 in isolated microtia. | Wang X et al. | — | 2024 | → |
| Histories of Dermatan Sulfate Epimerase and Dermatan 4-<i>O</i>-Sulfotransferase from Discovery of Their Enzymes and Genes to Musculocontractural Ehlers-Danlos Syndrome. | Mizumoto S et al. | — | 2023 | → |
| Mouse Models of Musculocontractural Ehlers-Danlos Syndrome. | Yoshizawa T et al. | — | 2023 | → |
| Otological Features of Patients with Musculocontractural Ehlers-Danlos Syndrome Caused by Pathogenic Variants in <i>CHST14</i> (mcEDS-<i>CHST14</i>). | Kawakita M et al. | — | 2023 | → |
| Rhegmatogenous Retinal Detachment in Musculocontractural Ehlers-Danlos Syndrome Caused by Biallelic Loss-of-Function Variants of Gene for Dermatan Sulfate Epimerase. | Yoshikawa Y et al. | — | 2023 | → |
| Case report: Multiple gastrointestinal perforations in a rare musculocontractural Ehlers-Danlos syndrome with multiple organ dysfunction. | Qian H et al. | — | 2022 | → |
| Clinical and molecular features of 66 patients with musculocontractural Ehlers-Danlos syndrome caused by pathogenic variants in <i>CHST14</i> (mcEDS-<i>CHST14</i>). | Minatogawa M et al. | — | 2022 | → |
| Clinical and pathophysiological delineation of musculocontractural Ehlers-Danlos syndrome caused by dermatan sulfate epimerase deficiency (mcEDS-DSE): A detailed and comprehensive glycobiological and pathological investigation in a novel patient. | Minatogawa M et al. | — | 2022 | → |
| Heat Shock Alters the Proteomic Profile of Equine Mesenchymal Stem Cells. | Abd-El-Aziz A et al. | — | 2022 | → |
| Supply chain logistics - the role of the Golgi complex in extracellular matrix production and maintenance. | Hellicar J et al. | — | 2022 | → |
| The Specific Role of Dermatan Sulfate as an Instructive Glycosaminoglycan in Tissue Development. | Mizumoto S et al. | — | 2022 | → |
| Adipocyte-specific deletion of HuR induces spontaneous cardiac hypertrophy and fibrosis. | Guarnieri AR et al. | — | 2021 | → |
| Animal Models of Ehlers-Danlos Syndromes: Phenotype, Pathogenesis, and Translational Potential. | Vroman R et al. | — | 2021 | → |
| A novel variant in the DSE gene leads to Ehlers-Danlos musculocontractural type 2 in a Pakistani family. | Ullah I et al. | — | 2021 | → |
| Chondrodysplasias With Multiple Dislocations Caused by Defects in Glycosaminoglycan Synthesis. | Dubail J et al. | — | 2021 | → |
| Congenital Disorders of Deficiency in Glycosaminoglycan Biosynthesis. | Mizumoto S et al. | — | 2021 | → |
| Ehlers Danlos Syndrome with Glycosaminoglycan Abnormalities. | Miyake N et al. | — | 2021 | → |
| Hypermobile Ehlers-Danlos syndromes: Complex phenotypes, challenging diagnoses, and poorly understood causes. | Gensemer C et al. | — | 2021 | → |
| Inherited Proteoglycan Biosynthesis Defects-Current Laboratory Tools and Bikunin as a Promising Blood Biomarker. | Haouari W et al. | — | 2021 | → |
| Myopathy Associated With Dermatan Sulfate-Deficient Decorin and Myostatin in Musculocontractural Ehlers-Danlos Syndrome: A Mouse Model Investigation. | Nitahara-Kasahara Y et al. | — | 2021 | → |
| The structure of human dermatan sulfate epimerase 1 emphasizes the importance of C5-epimerization of glucuronic acid in higher organisms. | Hasan M et al. | — | 2021 | → |
| A robust 11-genes prognostic model can predict overall survival in bladder cancer patients based on five cohorts. | Lin J et al. | — | 2020 | → |
| Delineation of musculocontractural Ehlers-Danlos Syndrome caused by dermatan sulfate epimerase deficiency. | Lautrup CK et al. | — | 2020 | → |
| DSE associated musculocontractural EDS, a milder phenotype or phenotypic variability. | Schirwani S et al. | — | 2020 | → |
| Hereditary Hearing Impairment with Cutaneous Abnormalities. | Lee TL et al. | — | 2020 | → |
| The Ehlers-Danlos syndromes. | Malfait F et al. | — | 2020 | → |
| Bone and connective tissue disorders caused by defects in glycosaminoglycan biosynthesis: a panoramic view. | Paganini C et al. | — | 2019 | → |
| DSE regulates the malignant characters of hepatocellular carcinoma cells by modulating CCL5/CCR1 axis. | Liao WC et al. | — | 2019 | → |
| Recent Advances in the Pathophysiology of Musculocontractural Ehlers-Danlos Syndrome. | Kosho T et al. | — | 2019 | → |
| Understanding the basis of Ehlers-Danlos syndrome in the era of the next-generation sequencing. | Cortini F et al. | — | 2019 | → |
| Dendritic Cell Migration to Skin-Draining Lymph Nodes Is Controlled by Dermatan Sulfate and Determines Adaptive Immunity Magnitude. | Nadafi R et al. | — | 2018 | → |
| Dermatan sulfate epimerase 1 and dermatan 4-<i>O</i>-sulfotransferase 1 form complexes that generate long epimerized 4-<i>O</i>-sulfated blocks. | Tykesson E et al. | — | 2018 | → |
| From Structure to Phenotype: Impact of Collagen Alterations on Human Health. | Arseni L et al. | — | 2018 | → |
| Gene expression of the two developmentally regulated dermatan sulfate epimerases in the Xenopus embryo. | Gouignard N et al. | — | 2018 | → |
| SLC10A7 mutations cause a skeletal dysplasia with amelogenesis imperfecta mediated by GAG biosynthesis defects. | Dubail J et al. | — | 2018 | → |
| Vascular aspects of the Ehlers-Danlos Syndromes. | Malfait F | — | 2018 | → |
| Vascular phenotypes in nonvascular subtypes of the Ehlers-Danlos syndrome: a systematic review. | D'hondt S et al. | — | 2018 | → |
| A genome wide association study of fast beta EEG in families of European ancestry. | Meyers JL et al. | — | 2017 | → |
| Chondrodysplasia with multiple dislocations: comprehensive study of a series of 30 cases. | Ranza E et al. | — | 2017 | → |
| Defect in dermatan sulfate in urine of patients with Ehlers-Danlos syndrome caused by a CHST14/D4ST1 deficiency. | Mizumoto S et al. | — | 2017 | → |
| [Ehlers-Danlos syndromes]. | Germain DP | — | 2017 | → |
| Genomic approaches to diagnose rare bone disorders. | Falardeau F et al. | — | 2017 | → |
| Modeling human craniofacial disorders in <i>Xenopus</i>. | Dubey A et al. | — | 2017 | → |
| Pathophysiological Significance of Dermatan Sulfate Proteoglycans Revealed by Human Genetic Disorders. | Mizumoto S et al. | — | 2017 | → |
| The Ehlers-Danlos syndromes, rare types. | Brady AF et al. | — | 2017 | → |
| Biosynthesis of glycosaminoglycans: associated disorders and biochemical tests. | Sasarman F et al. | — | 2016 | → |
| CHST14/D4ST1 deficiency: New form of Ehlers-Danlos syndrome. | Kosho T | — | 2016 | → |
| Deciphering the Mode of Action of the Processive Polysaccharide Modifying Enzyme Dermatan Sulfate Epimerase 1 by Hydrogen-Deuterium Exchange Mass Spectrometry. | Tykesson E et al. | — | 2016 | → |
| Glycosaminoglycan and proteoglycan in skin aging. | Lee DH et al. | — | 2016 | → |
| Musculocontractural Ehlers-Danlos syndrome and neurocristopathies: dermatan sulfate is required for Xenopus neural crest cells to migrate and adhere to fibronectin. | Gouignard N et al. | — | 2016 | → |
| The phenotype of the musculocontractural type of Ehlers-Danlos syndrome due to CHST14 mutations. | Janecke AR et al. | — | 2016 | → |
| Chondroitin / dermatan sulfate modification enzymes in zebrafish development. | Habicher J et al. | — | 2015 | → |
| Dermatan Sulfate-Free Mice Display Embryological Defects and Are Neonatal Lethal Despite Normal Lymphoid and Non-Lymphoid Organogenesis. | Stachtea XN et al. | — | 2015 | → |
| Differential diagnosis and diagnostic flow chart of joint hypermobility syndrome/ehlers-danlos syndrome hypermobility type compared to other heritable connective tissue disorders. | Colombi M et al. | — | 2015 | → |
| Ehlers-Danlos Syndrome, Hypermobility Type, Is Linked to Chromosome 8p22-8p21.1 in an Extended Belgian Family. | Syx D et al. | — | 2015 | → |
| Genetic heterogeneity and clinical variability in musculocontractural Ehlers-Danlos syndrome caused by impaired dermatan sulfate biosynthesis. | Syx D et al. | — | 2015 | → |
| Insights in the etiopathology of galactosyltransferase II (GalT-II) deficiency from transcriptome-wide expression profiling of skin fibroblasts of two sisters with compound heterozygosity for two novel <i>B3GALT6</i> mutations. | Ritelli M et al. | — | 2015 | → |
| The Genetics of Soft Connective Tissue Disorders. | Vanakker O et al. | — | 2015 | → |
| The neuromuscular differential diagnosis of joint hypermobility. | Donkervoort S et al. | — | 2015 | → |
| Dermatan sulfate epimerase 1 deficient mice as a model for human abdominal wall defects. | Gustafsson R et al. | — | 2014 | → |
| Human genetic disorders and knockout mice deficient in glycosaminoglycan. | Mizumoto S et al. | — | 2014 | → |