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Elevation of glycosaminoglycans in the amniotic fluid of a fetus with mucopolysaccharidosis VII
Author(s) -
Kubaski Francyne,
BrusiusFacchin Ana Carolina,
Mason Robert W.,
Patel Pravin,
Burin Maira G.,
MichelinTirelli Kristiane,
Kessler Rejane Gus,
Bender Fernanda,
LeistnerSegal Sandra,
Moreno Carolina A.,
Cavalcanti Denise P.,
Giugliani Roberto,
Tomatsu Shunji
Publication year - 2017
Publication title -
prenatal diagnosis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.956
H-Index - 97
eISSN - 1097-0223
pISSN - 0197-3851
DOI - 10.1002/pd.5028
Subject(s) - dermatan sulfate , heparan sulfate , keratan sulfate , amniotic fluid , glycosaminoglycan , chondroitin sulfate , hunter syndrome , fetus , chemistry , chondroitin , mucopolysaccharidosis , medicine , biochemistry , microbiology and biotechnology , biology , pregnancy , genetics
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. © 2017 John Wiley & Sons, Ltd.