title: Defect in dermatan sulfate in urine of patients with Ehlers-Danlos syndrome caused by a CHST14/D4ST1 deficiency.
abstract: OBJECTIVE
  Dermatan sulfate (DS) plays a number of roles in a wide range of biological activities such as cell signaling and tissue morphogenesis through interactions with various extracellular matrix proteins including collagen. Mutations in the carbohydrate sulfotransferase 14 gene (CHST14) encoding CHST14/dermatan 4-O-sulfotransferase-1 (D4ST1), which is responsible for the biosynthesis of DS, cause a recently delineated form of Ehlers-Danlos syndrome (EDS, musculocontractural type 1), an autosomal recessive connective tissue disorder characterized by congenital malformations (specific craniofacial features, and congenital multiple contractures) and progressive fragility-related complications (skin hyperextensibility, bruisability, and fragility with atrophic scars; recurrent dislocations; progressive talipes or spinal deformities; and large subcutaneous hematomas). In an attempt to develop a diagnostic screening method for this type of EDS, the amount of DS in the urine of patients was analyzed.
  
  
  METHODS
  Urinary DS was quantified by an anion-exchange chromatography after treatment with DS-specific degrading enzyme.
  
  
  RESULTS
  DS was not detected in the urine of patients with homo- or compound heterozygous mutations in CHST14. These results suggest that the quantification of DS in urine is applicable to an initial diagnosis of DS-defective EDS.
  
  
  CONCLUSIONS
  This is the first study to perform a urinary disaccharide compositional analysis of chondroitin sulfate (CS)/DS chains in patients with EDS caused by a CHST14/D4ST1 deficiency, and demonstrated the absence of DS chains. This result suggests systemic DS depletion in this disorder, and also proposes the usefulness of a urinary disaccharide compositional analysis of CS/DS chains as a non-invasive screening method for this disorder.
authors.affiliation: Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan. Electronic address: mizumoto@meijo-u.ac.jp.
authors.forename: Shuji
authors.initials: S
authors.lastname: Mizumoto
authors.affiliation: Center for Medical Genetics, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kosho
authors.affiliation: Department of Dermatology, Dokkyo Medical University, School of Medicine, 880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hatamochi
authors.affiliation: Laboratory of Proteoglycan Signaling and Therapeutics, Graduate School of Life Science Hokkaido University, Sapporo 001-0021, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Honda
authors.affiliation: Center for Medical Genetics, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka 594-1101, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.affiliation: Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan; Laboratory of Proteoglycan Signaling and Therapeutics, Graduate School of Life Science Hokkaido University, Sapporo 001-0021, Japan. Electronic address: k-sugar@sci.hokudai.ac.jp.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Sugahara
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002852:Chromatography, Ion Exchange; D003871:Dermatan Sulfate / Q000652:urine*; D004535:Ehlers-Danlos Syndrome / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000652:urine; D015870:Gene Expression; D006579:Heterozygote; D006801:Humans; D006868:Hydrolysis; D007223:Infant; D009154:Mutation; D015238:Sulfotransferases / Q000172:deficiency* / Q000235:genetics
chemical_list: D015415:Biomarkers; D003871:Dermatan Sulfate; D015238:Sulfotransferases; C438013:dermatan-4-sulfotransferase-1
keywords: Carbohydrate sulfotransferase 14; Chondroitin sulfate; Dermatan 4-O-sulfotransferase; Dermatan sulfate; Ehlers-Danlos syndrome; Urine