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Deep Genotyping of the IDS Gene in Colombian Patients with Hunter Syndrome

  • Johanna GalvisEmail author
  • Jannet González
  • Alfredo Uribe
  • Harvy Velasco
Research Report
Part of the JIMD Reports book series (JIMD, volume 19)

Abstract

Background: Mucopolysaccharidosis type II (MPSII), also known as Hunter syndrome, is an X-linked disorder caused by mutations in the iduronate 2 sulfatase (IDS) gene. This enzyme catalyzes the initial step in the catabolism of heparan sulfate and dermatan sulfate; thus, its deficiency leads to the accumulation of these glycosaminoglycans. MPS II has significant allelic heterogeneity, making the establishment of genotype-phenotype correlations difficult. This study assessed clinical features in combination with deep genotyping of a group of Colombian patients with MPS II and attempted to establish a degree of genotype-phenotype correlation by employing bioinformatic tools.

Methods: Eighteen patients were included in this study, 11% of whom were non-neuronopathic, and the other 89% were neuronopathic. Samples were all analyzed using three molecular methodologies: MLPA, direct exon sequencing, and RFLP analysis.

Results: A total of 13 mutations were identified, 6 of which were novel (c.548_564dup16, c.477insT, c.595_607del12, c. 549_562del13, c.182delC, and a complete deletion of exon 7). The frequency of common mutations (R468Q, Q465X, K347Q, K236N, S71N, R88H, and a conversion phenomenon) was 53.85%. The S71N mutation was frequent among the attenuated phenotype, while private frameshift mutations and rearrangements were seen in patients with severe phenotypes. Molecular docking was performed on the wild-type and mutant IDS proteins, which revealed changes in the enzyme-substrate interaction for the mutant IDS.

Conclusion: The frequency of novel mutations (46.15%) is similar to what has been reported elsewhere. The use of bioinformatic tools showed differences in enzyme-substrate interactions. Studies with larger groups of patients are needed.

Keywords

Bioinformatic analysis Colombian patients Iduronate sulfatase Molecular docking Mucopolysaccharidosis II 

Notes

Acknowledgments

To patients and their families, MRC-Holland for the donation of the MLPA kit for this research, ACOPEL, and Doctors Gabriel Sierra, Luz Norella Correa, Gustavo Contreras, Sandra Mansilla, and Juan Carlos Prieto. To professors Mauricio Rey, Rita Baldrich, Blanca Schroeder, Henry J Rodríguez, and other members of immunogenetics/biology group at Universidad Nacional de Colombia for their support relating to laboratory work. To Tatiana Vinasco, David Serrano, and Andres Gutierrez for contribution of literature and counseling.

Supplementary material

334361_1_En_376_MOESM1_ESM.doc (84 kb)
(DOC 84 kb)

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Johanna Galvis
    • 1
    Email author
  • Jannet González
    • 2
  • Alfredo Uribe
    • 3
  • Harvy Velasco
    • 4
  1. 1.Master’s Program in Human GeneticsNational University of ColombiaBogotáColombia
  2. 2.Nutrition and Biochemistry LaboratoryPontifical Xaverian UniversityBogotáColombia
  3. 3.Biochemical Investigations Centre (CIBI)University of Los AndesBogotáColombia
  4. 4.Master’s Program in Human GeneticsNational University of ColombiaBogotáColombia

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