Special Issue "Musculocontractural Ehlers-Danlos Syndrome and the Biological Role of Dermatan Sulfate"

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (10 December 2022) | Viewed by 1441

Special Issue Editors

Prof. Dr. Tomoki Kosho
E-Mail Website
Guest Editor
1. Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
2. Center for Medical Genetics, Shinshu University Hospital, Matsumoto 390-8621, Japan
3. Research Center for Supports to Advanced Science, Matsumoto 390-8621, Japan
4. Division of Clinical Sequencing, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
Interests: Ehlers-Danlos syndrome; medical genetics; human genetics
Dr. Shuji Mizumoto
E-Mail Website
Guest Editor
Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, Nagoya 468-8503, Japan
Interests: proteoglycan; glycosaminoglycan; chondroitin sulfate; dermatan sulfate; heparan sulfate; Ehlers–Danlos syndrome; spondyloepimetaphyseal dysplasia

Special Issue Information

Dear Colleagues, 

Ehlers−Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of heritable connective tissue disorders characterized by skin hyperextensibility, joint hypermobility and tissue fragility. The 2017 International Classification of EDS identified 13 subtypes based on their clinical and genetic backgrounds, among them musculocontractural Ehlers–Danlos syndrome (mcEDS), caused by biallelic loss-of-function variants either in the gene for carbohydrate sulfotransferase 14/dermatan 4-O-sulfotransferase 1 (CHST14/D4ST1, mcEDS-CHST14) (MIM#601776) or that for dermatan sulfate epimerase (DSE, mcEDS-DSE) (MIM#615539). Dermatan sulfate depletion through impaired activities of D4ST1 or DSE constitutes the basis of the disorder. To date, 66 patients (48 families) and 13 patients (7 families) with mcEDS-CHST14 and mcEDS-DSE , respectively, have been reported. Clinical characteristics include multiple malformations (e.g., craniofacial features, multiple congenital contractures, ocular and visceral malformations) and progressive fragility-related manifestations (e.g., skin hyperextensibility and fragility, joint hypermobility with luxation, progressive spinal and foot deformities, large subcutaneous hematoma and visceral ruptures). This is a human condition that affects the biosynthesis of dermatan sulfate, a side chain of proteoglycans; therefore, clinical, genetic, biochemical, glycobiological and pathological investigation of the disorder could elucidate dermatan sulfate proteoglycans’ fundamental biological roles in fetal development and maintenance of the connective tissue system. This Special Issue will feature a detailed overview of the latest clinical research and relevant findings as well as a comprehensive review of the literature on Ehlers–Danlos syndrome or dermatan sulfate biosynthesis. These findings would be helpful not only to clinicians involved in the management of hereditary connective tissue disorders but also scientists interested in the biological and pathological roles of dermatan sulfate proteoglycan.

Prof. Dr. Tomoki Kosho
Dr. Shuji Mizumoto
Guest Editors

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Keywords

  • musculocontractural Ehlers–Danlos syndrome
  • dermatan sulfate
  • dermatan 4-O-sulfotransferase
  • dermatan sulfate epimerase
  • decorin
  • collagen fibril network
  • genetics
  • glycobiology
  • proteoglycan

Published Papers (2 papers)

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Research

Article
Collagen Network Formation in In Vitro Models of Musculocontractural Ehlers–Danlos Syndrome
Genes 2023, 14(2), 308; https://doi.org/10.3390/genes14020308 - 24 Jan 2023
Viewed by 394
Abstract
Loss-of-function mutations in carbohydrate sulfotransferase 14 (CHST14) cause musculocontractural Ehlers–Danlos syndrome-CHST14 (mcEDS-CHST14), characterized by multiple congenital malformations and progressive connective tissue fragility-related manifestations in the cutaneous, skeletal, cardiovascular, visceral and ocular system. The replacement of dermatan sulfate chains [...] Read more.
Loss-of-function mutations in carbohydrate sulfotransferase 14 (CHST14) cause musculocontractural Ehlers–Danlos syndrome-CHST14 (mcEDS-CHST14), characterized by multiple congenital malformations and progressive connective tissue fragility-related manifestations in the cutaneous, skeletal, cardiovascular, visceral and ocular system. The replacement of dermatan sulfate chains on decorin proteoglycan with chondroitin sulfate chains is proposed to lead to the disorganization of collagen networks in the skin. However, the pathogenic mechanisms of mcEDS-CHST14 are not fully understood, partly due to the lack of in vitro models of this disease. In the present study, we established in vitro models of fibroblast-mediated collagen network formation that recapacitate mcEDS-CHST14 pathology. Electron microscopy analysis of mcEDS-CHST14-mimicking collagen gels revealed an impaired fibrillar organization that resulted in weaker mechanical strength of the gels. The addition of decorin isolated from patients with mcEDS-CHST14 and Chst14−/− mice disturbed the assembly of collagen fibrils in vitro compared to control decorin. Our study may provide useful in vitro models of mcEDS-CHST14 to elucidate the pathomechanism of this disease. Full article
Article
Clinical Presentation and Characteristics of the Upper Extremity in Patients with Musculocontractural Ehlers–Danlos Syndrome
Genes 2022, 13(11), 1978; https://doi.org/10.3390/genes13111978 - 29 Oct 2022
Viewed by 674
Abstract
Musculocontractural Ehlers–Danlos syndrome (mcEDS) is a subtype of EDS caused by defective dermatan sulfate biosynthesis, characterized by multiple malformations (craniofacial features, ocular and visceral malformations) and progressive cutaneous, skeletal, vascular, and visceral fragility-related manifestations. Repeated dislocations and deformities of the joints due to [...] Read more.
Musculocontractural Ehlers–Danlos syndrome (mcEDS) is a subtype of EDS caused by defective dermatan sulfate biosynthesis, characterized by multiple malformations (craniofacial features, ocular and visceral malformations) and progressive cutaneous, skeletal, vascular, and visceral fragility-related manifestations. Repeated dislocations and deformities of the joints due to joint relaxation are observed, causing serious damage to the musculoskeletal system of the whole body; however, the motor function of the upper limbs and the morphology of the bone joints have not been systematically investigated. In this study, we present a detailed and comprehensive report on upper limb lesions of 13 patients with a mean age at the first visit of 21 years. Twelve patients (92.3%) had a history of dislocation. Eleven patients (84.6%) had shoulder dislocations, and two patients (15.4%) had elbow dislocations. Four patients (30.8%) had elbow osteoarthritis, and three patients (23.1%) had distal radioulnar joint (DRUJ) osteoarthritis. The phalanges and metacarpals are thin, and the ratio of medullary cavity of the metacarpal bone decreases with age. As bone and joint deformity progresses, patients with mcEDS should be recommended to receive regular follow-up, including radiology. The present findings suggest an important role for dermatan sulfate in the maintenance of the skeletal system. Full article
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