Francyne Kubaski1,2,3, Ana Carolina Brusius-Facchin4, Robert W Mason1,2, Pravin Patel5, Maira G Burin4, Kristiane Michelin-Tirelli4, Rejane Gus Kessler4, Fernanda Bender4, Sandra Leistner-Segal4,6, Carolina A Moreno7, Denise P Cavalcanti7, Roberto Giugliani3,4,6,8, Shunji Tomatsu1,2. 1. Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA. 2. Department of Biological Sciences, University of Delaware, Newark, DE, USA. 3. INAGEMP, Porto Alegre, Rio Grande do Sul, Brazil. 4. Medical Genetics Service, HCPA, Porto Alegre, Rio Grande do Sul, Brazil. 5. Graduate School of Biomedical Sciences, Thomas Jefferson University, Philadelphia, PA, USA. 6. Post Graduation Program on Medical Sciences, UFRGS, Porto Alegre, Rio Grande do Sul, Brazil. 7. Perinatal Genetic Program, Department of Medical Genetics, UNICAMP, Campinas, Campinas, SP, Brazil. 8. Department of Genetics, UFRGS, Porto Alegre, Rio Grande do Sul, Brazil.
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. METHOD: 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). CONCLUSION: 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.
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. METHOD: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). CONCLUSION: 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.
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