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. 2015:19:101-9.
doi: 10.1007/8904_2014_376. Epub 2015 Feb 15.

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

Johanna Galvis  1 , Jannet González, Alfredo Uribe, Harvy Velasco
Affiliations

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

Johanna Galvis et al. JIMD Rep. 2015.

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.

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Figures

Fig. 1
Fig. 1
Complete deletion of exon 7 in patient MPSII012. The X-axis of this bar diagram displays specific fragments, and the Y-axis shows normalized ratios. The fragment for exon 7 (7) yielded no signal (0)
Fig. 2
Fig. 2
PCR 2 products after digestion with AcuI. C control. Note the 1,174 bp product on well 3, corresponding to MPSII013. M molecular weight
See this image and copyright information in PMC

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