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

BMC Med Genet. 2020 May 24;21(1):111. doi: 10.1186/s12881-020-01051-9.

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.

Keywords: Clinical features; Hunter syndrome; Mucopolysaccharidosis type II; Mutations.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Enzyme Activation
  • Female
  • Genetic Association Studies* / methods
  • Genetic Predisposition to Disease*
  • Glycoproteins / genetics*
  • Glycosaminoglycans / metabolism
  • Glycosaminoglycans / urine
  • Humans
  • Infant
  • Male
  • Mucopolysaccharidosis II / diagnosis*
  • Mucopolysaccharidosis II / epidemiology
  • Mucopolysaccharidosis II / genetics*
  • Mucopolysaccharidosis II / metabolism
  • Mutation*
  • Phenotype
  • Tunisia / epidemiology
  • Young Adult

Substances

  • Glycoproteins
  • Glycosaminoglycans
  • IDS protein, human