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The mutational spectrum of hunter syndrome reveals correlation between biochemical and clinical profiles in Tunisian patients
BACKGROUND: Mucopolysaccharidosis type II (MPS II) or Hunter syndrome is an X-linked recessive lysosomal storage disorder resulting from deficient activity of iduronate 2-sulfatase (IDS) and the progressive lysosomal accumulation of sulfated glycosaminoglycans (GAGs). METHODS: A diagnosis of MPS II...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247178/ https://www.ncbi.nlm.nih.gov/pubmed/32448126 http://dx.doi.org/10.1186/s12881-020-01051-9 |
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author | Chkioua, L Grissa, O Leban, N Gribaa, M Boudabous, H Turkia, H Ben Ferchichi, S Tebib, N Laradi, S |
author_facet | Chkioua, L Grissa, O Leban, N Gribaa, M Boudabous, H Turkia, H Ben Ferchichi, S Tebib, N Laradi, S |
author_sort | Chkioua, L |
collection | PubMed |
description | BACKGROUND: Mucopolysaccharidosis type II (MPS II) or Hunter syndrome is an X-linked recessive lysosomal storage disorder resulting from deficient activity of iduronate 2-sulfatase (IDS) and the progressive lysosomal accumulation of sulfated glycosaminoglycans (GAGs). METHODS: A diagnosis of MPS II or Hunter syndrome was performed based on the following approach after a clinical and paraclinical suspicion. Two biochemical and molecular tests were carried out separately and according to the availability of the biological material. RESULTS: All patients in this cohort presented the most common MPS II clinical features. Electrophoresis of GAGs on a cellulose acetate plate in the presence of a high concentration of heparane sulfate showed an abnormal dermatan sulfate band in the patients compared with that in a control case. Furthermore, leukocyte IDS activity ranged from 0.00 to 0.75 nmol/h/mg of leukocyte protein in patients. Five previously reported mutations were identified in this study patients: one splice site mutation, c.240 + 1G > A; two missense mutations, p.R88P and p.G94D; a large deletion of exon 1 to exon 7; and one nonsense mutation, p.Q396*. In addition, two novel alterations were identified in the MPS II patients: one frame shift mutation, p.D450Nfs*95 and one nonsense mutation, p.Q204*. Additionally, five known IDS polymorphisms were identified in the patients: c.419–16 delT, c.641C > T (p.T214M), c.438 C > T (p.T146T), c.709-87G > A, and c.1006 + 38 T > C. CONCLUSIONS: The high level of urine GAGs and the deficiency of iduronate 2-sulfatase activity was associated with the phenotype expression of Hunter syndrome. Molecular testing was useful for the patients’ phenotypic classification and the detection of carriers. |
format | Online Article Text |
id | pubmed-7247178 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-72471782020-06-01 The mutational spectrum of hunter syndrome reveals correlation between biochemical and clinical profiles in Tunisian patients Chkioua, L Grissa, O Leban, N Gribaa, M Boudabous, H Turkia, H Ben Ferchichi, S Tebib, N Laradi, S BMC Med Genet Research Article BACKGROUND: Mucopolysaccharidosis type II (MPS II) or Hunter syndrome is an X-linked recessive lysosomal storage disorder resulting from deficient activity of iduronate 2-sulfatase (IDS) and the progressive lysosomal accumulation of sulfated glycosaminoglycans (GAGs). METHODS: A diagnosis of MPS II or Hunter syndrome was performed based on the following approach after a clinical and paraclinical suspicion. Two biochemical and molecular tests were carried out separately and according to the availability of the biological material. RESULTS: All patients in this cohort presented the most common MPS II clinical features. Electrophoresis of GAGs on a cellulose acetate plate in the presence of a high concentration of heparane sulfate showed an abnormal dermatan sulfate band in the patients compared with that in a control case. Furthermore, leukocyte IDS activity ranged from 0.00 to 0.75 nmol/h/mg of leukocyte protein in patients. Five previously reported mutations were identified in this study patients: one splice site mutation, c.240 + 1G > A; two missense mutations, p.R88P and p.G94D; a large deletion of exon 1 to exon 7; and one nonsense mutation, p.Q396*. In addition, two novel alterations were identified in the MPS II patients: one frame shift mutation, p.D450Nfs*95 and one nonsense mutation, p.Q204*. Additionally, five known IDS polymorphisms were identified in the patients: c.419–16 delT, c.641C > T (p.T214M), c.438 C > T (p.T146T), c.709-87G > A, and c.1006 + 38 T > C. CONCLUSIONS: The high level of urine GAGs and the deficiency of iduronate 2-sulfatase activity was associated with the phenotype expression of Hunter syndrome. Molecular testing was useful for the patients’ phenotypic classification and the detection of carriers. BioMed Central 2020-05-24 /pmc/articles/PMC7247178/ /pubmed/32448126 http://dx.doi.org/10.1186/s12881-020-01051-9 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Chkioua, L Grissa, O Leban, N Gribaa, M Boudabous, H Turkia, H Ben Ferchichi, S Tebib, N Laradi, S The mutational spectrum of hunter syndrome reveals correlation between biochemical and clinical profiles in Tunisian patients |
title | The mutational spectrum of hunter syndrome reveals correlation between biochemical and clinical profiles in Tunisian patients |
title_full | The mutational spectrum of hunter syndrome reveals correlation between biochemical and clinical profiles in Tunisian patients |
title_fullStr | The mutational spectrum of hunter syndrome reveals correlation between biochemical and clinical profiles in Tunisian patients |
title_full_unstemmed | The mutational spectrum of hunter syndrome reveals correlation between biochemical and clinical profiles in Tunisian patients |
title_short | The mutational spectrum of hunter syndrome reveals correlation between biochemical and clinical profiles in Tunisian patients |
title_sort | mutational spectrum of hunter syndrome reveals correlation between biochemical and clinical profiles in tunisian patients |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247178/ https://www.ncbi.nlm.nih.gov/pubmed/32448126 http://dx.doi.org/10.1186/s12881-020-01051-9 |
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