The mutational spectrum of hunter syndrome reveals correlation between biochemical and clinical profiles in Tunisian patients
Abstract 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...
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BMC
2020-05-01
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| Series: | BMC Medical Genetics |
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| Online Access: | http://link.springer.com/article/10.1186/s12881-020-01051-9 |
| _version_ | 1818741480615837696 |
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| author | L Chkioua O Grissa N Leban M Gribaa H Boudabous H Ben Turkia S Ferchichi N Tebib S Laradi |
| author_facet | L Chkioua O Grissa N Leban M Gribaa H Boudabous H Ben Turkia S Ferchichi N Tebib S Laradi |
| author_sort | L Chkioua |
| collection | DOAJ |
| description | Abstract 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. |
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| institution | Directory Open Access Journal |
| issn | 1471-2350 |
| language | English |
| last_indexed | 2024-12-18T01:57:18Z |
| publishDate | 2020-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genetics |
| spelling | doaj.art-d9b82ed64b4b4461b72229473e81b5842022-12-21T21:24:53ZengBMCBMC Medical Genetics1471-23502020-05-0121111010.1186/s12881-020-01051-9The mutational spectrum of hunter syndrome reveals correlation between biochemical and clinical profiles in Tunisian patientsL Chkioua0O Grissa1N Leban2M Gribaa3H Boudabous4H Ben Turkia5S Ferchichi6N Tebib7S Laradi8Research Laboratory of Human Genome and Multifactorial Diseases, Faculty of Pharmacy, University of MonastirResearch Laboratory of Human Genome and Multifactorial Diseases, Faculty of Pharmacy, University of MonastirResearch Laboratory of Human Genome and Multifactorial Diseases, Faculty of Pharmacy, University of MonastirDepartment of Cytogenetic and Reproductive Biology Farhat HACHED HospitalLaboratory of pediatrics, La Rabta Hospital TunisLaboratory of pediatrics, La Rabta Hospital TunisBiochemistry Laboratory, Farhat HACHED Hospital SousseLaboratory of pediatrics, La Rabta Hospital TunisThe Auvergne-Rhône-Alpes Regional Branch of the French National Blood System EFS/GIMAP-EA 3064Abstract 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.http://link.springer.com/article/10.1186/s12881-020-01051-9Mucopolysaccharidosis type IIHunter syndromeClinical featuresMutations |
| spellingShingle | L Chkioua O Grissa N Leban M Gribaa H Boudabous H Ben Turkia S Ferchichi N Tebib S Laradi The mutational spectrum of hunter syndrome reveals correlation between biochemical and clinical profiles in Tunisian patients BMC Medical Genetics Mucopolysaccharidosis type II Hunter syndrome Clinical features Mutations |
| 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 | Mucopolysaccharidosis type II Hunter syndrome Clinical features Mutations |
| url | http://link.springer.com/article/10.1186/s12881-020-01051-9 |
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