Ferrer, Alejandro, Tzovenos Starosta, Rodrigo, Ranatunga, Wasantha et al. (6 more authors) (2020) Fetal glycosylation defect due to ALG3 and GOG5 variants detected via amniocentesis:complex glycosylation defect with embryonic lethal phenotype. Molecular genetics and metabolism. pp. 424-429. ISSN 1096-7192
Abstract
Introduction Congenital disorders of glycosylation (CDG) are inborn errors of glycan metabolism with high clinical variability. Only a few antenatal cases have been described with CDG. Due to a lack of reliable biomarker, prenatal CDG diagnostics relies primarily on molecular studies. In the presence of variants of uncertain significance prenatal glycosylation studies are very challenging. Case report A consanguineous couple had a history of second-trimester fetal demise with tetralogy of Fallot and skeletal dysplasia. In the consecutive pregnancy, the second trimester ultrasonography showed skeletal dysplasia, vermian hypoplasia, congenital heart defects, omphalocele and dysmorphic features. Prenatal chromosomal microarray revealed a large region of loss of heterozygosity. Demise occurred at 30 weeks. Fetal whole exome sequencing showed a novel homozygous likely pathogenic variant in ALG3 and a variant of uncertain significance in COG5. Methods Western blot was used to quantify ALG3, COG5, COG6, and the glycosylation markers ICAM-1 and LAMP2. RT-qPCR was used for ALG3 and COG5 expression in cultured amniocytes and compared to age matched controls. Results ALG3 and COG5 mRNA levels were normal. ICAM-1, LAMP2, ALG3 and COG5 levels were decreased in cultured amniocytes, suggesting the possible involvement of both genes in the complex phenotype. Conclusion This is the first case of successful use of glycosylated biomarkers in amniocytes, providing further options of functional antenatal testing in CDG.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 Published by Elsevier Inc. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 18 Nov 2020 10:40 |
Last Modified: | 21 Jan 2025 17:50 |
Published Version: | https://doi.org/10.1016/j.ymgme.2020.11.003 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1016/j.ymgme.2020.11.003 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:168123 |