The mutational spectrum of hunter syndrome reveals correlation between biochemical and clinical profiles in Tunisian patients

• Published in: BMC medical genetics Vol. 21; no. 1; p. 111
• Main Authors: Chkioua, L, Grissa, O, Leban, N, Gribaa, M, Boudabous, H, Turkia, H Ben, Ferchichi, S, Tebib, N, Laradi, S
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 24-05-2020; BioMed Central; BMC
• Subjects: Acetic acid; Age; Biochemistry; Cellulose; Cellulose acetate; Clinical features; Deoxyribonucleic acid; Diagnosis; Disease; DNA; Enzymes; Family medical history; Gene deletion; Genetic aspects; Glycosaminoglycans; Heparan sulfate; Hereditary diseases; Hunter syndrome; Laboratories; Medical research; Missense mutation; Mucopolysaccharides; Mucopolysaccharidoses; Mucopolysaccharidosis; Mucopolysaccharidosis type II; Mutation; Mutations; Nonsense mutation; Patients; Phenotypes; Proteins; Sulfate; Sulfates; Tunisia; Mucopolysaccharidosis type II; Hunter syndrome; Mutations; Clinical features
• ISSN: 1471-2350; 1471-2350
• DOI: 10.1186/s12881-020-01051-9

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).
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.
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.
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.