title: Elevation of glycosaminoglycans in the amniotic fluid of a fetus with mucopolysaccharidosis VII.
abstract: OBJECTIVE
  The aim of this study was to quantify glycosaminoglycans (GAGs) in amniotic fluid (AF) from an MPS VII fetus compared with age-matched fetuses obtained from normal pregnancies.
  
  
  METHODS
  Disaccharides were measured by liquid chromatography tandem mass spectrometry, compared to age-matched controls. Enzyme assay was performed in AF supernatant or cultured amniocytes. GUSB was analyzed by next generation sequencing using Ion Torrent Personal Genome Machine with a customized panel.
  
  
  RESULTS
  No activity of β-glucuronidase was detected in fetal cells. The pregnancy was spontaneously terminated in the third trimester. Genetic studies identified a homozygous mutation of p.N379D (c.1135A > G) in the GUSB gene. Liquid chromatography tandem mass spectrometry showed that chondroitin sulfate, dermatan sulfate, heparan sulfate, and keratan sulfate levels were markedly increased in the MPS VII AF, compared to those in age-matched control AF (dermatan sulfate, heparan sulfate, and chondroitin-6-sulfate more than 10 × than age-matched controls; chondroitin-4-sulfate and keratan sulfate more than 3 times higher).
  
  
  CONCLUSIONS
  This is the first report of specific GAG analysis in AF from an MPS VII fetus, indicating that GAG elevation in AF occurs by 21 weeks of gestation and could be an additional tool for prenatal diagnosis of MPS VII and potentially other MPS types. © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA.|Department of Biological Sciences, University of Delaware, Newark, DE, USA.|INAGEMP, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Francyne
authors.identifier: http://orcid.org/0000-0002-9330-0154
authors.initials: F
authors.lastname: Kubaski
authors.affiliation: Medical Genetics Service, HCPA, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Brusius-Facchin
authors.affiliation: Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA.|Department of Biological Sciences, University of Delaware, Newark, DE, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Mason
authors.affiliation: Graduate School of Biomedical Sciences, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Pravin
authors.initials: P
authors.lastname: Patel
authors.affiliation: Medical Genetics Service, HCPA, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Maira G
authors.initials: MG
authors.lastname: Burin
authors.affiliation: Medical Genetics Service, HCPA, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Kristiane
authors.initials: K
authors.lastname: Michelin-Tirelli
authors.affiliation: Medical Genetics Service, HCPA, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Rejane Gus
authors.initials: RG
authors.lastname: Kessler
authors.affiliation: Medical Genetics Service, HCPA, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Bender
authors.affiliation: Medical Genetics Service, HCPA, Porto Alegre, Rio Grande do Sul, Brazil.|Post Graduation Program on Medical Sciences, UFRGS, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Sandra
authors.initials: S
authors.lastname: Leistner-Segal
authors.affiliation: Perinatal Genetic Program, Department of Medical Genetics, UNICAMP, Campinas, Campinas, SP, Brazil.
authors.forename: Carolina A
authors.initials: CA
authors.lastname: Moreno
authors.affiliation: Perinatal Genetic Program, Department of Medical Genetics, UNICAMP, Campinas, Campinas, SP, Brazil.
authors.forename: Denise P
authors.initials: DP
authors.lastname: Cavalcanti
authors.affiliation: INAGEMP, Porto Alegre, Rio Grande do Sul, Brazil.|Medical Genetics Service, HCPA, Porto Alegre, Rio Grande do Sul, Brazil.|Post Graduation Program on Medical Sciences, UFRGS, Porto Alegre, Rio Grande do Sul, Brazil.|Department of Genetics, UFRGS, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.affiliation: Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA.|Department of Biological Sciences, University of Delaware, Newark, DE, USA.
authors.forename: Shunji
authors.initials: S
authors.lastname: Tomatsu
mesh_terms: D000328:Adult; D000653:Amniotic Fluid / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D005315:Fetal Diseases / Q000378:metabolism* / Q000473:pathology; D005333:Fetus / Q000378:metabolism* / Q000473:pathology; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D016538:Mucopolysaccharidosis VII / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D015854:Up-Regulation
chemical_list: D006025:Glycosaminoglycans