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Molecular analysis of the iduronate-2-sulfatase gene in Thai patients with Hunter syndrome

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Journal of Inherited Metabolic Disease

Summary

Molecular defects in the gene encoding the enzyme iduronate-2-sulfatase (IDS) result in Hunter disease (mucopolysaccharidosis type II, MPS II). To determine the molecular basis of MPS II in Thailand, the IDS gene was analysed in 20 Thai patients with Hunter syndrome from 18 unrelated families. A total of 19 different mutations, including 9 missense mutations, 3 nonsense mutations, 3 splice site alterations, 1 deletion, 2 indels, and 1 rearrangement were identified, 8 of which were novel (p.R101C, p.D148V, p.G224A, p.K227E, p.E254X, p.W337X, c.440_442delinsTT and c.720_731delinsTTTCAGATGTTCTCCCCAG). Evaluation of the IDS activity of two hemizygous variants identified in the same patient, p.R101C and p.R468Q, by expression of IDS with the individual mutations in COS 7 cells indicated that only the p.R468Q mutation affected IDS protein activity. Two exonic mutations, c.257C>T (p.P86L) and c.418G>A, were found to activate multiple cryptic splice sites, resulting in aberrantly spliced transcripts. Thus, MPS II in Thailand is caused by a diverse set of defects affecting both IDS protein production and activity.

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Fig. 1
Fig. 2

Abbreviations

ESE:

exonic splicing enhancer

IDS:

iduronate 2-sulfatase

IDS :

iduronate 2-sulfatase gene

IDS-2 :

iduronate 2-sulfatase pseudogene

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Acknowledgements

The authors are grateful to the families of the patients for their assistance in this investigation and to the Chulabhorn Research Institute and Mahidol University for financial support. J.S. is a Senior Research Scholar of the Thailand Research Fund. D.W. and P.S. are recipients of Research Career Development Awards from the Faculty of Medicine, Ramathibodi Hospital, Mahidol University.

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Authors and Affiliations

  1. Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok, 10210, Thailand

    S. Keeratichamroen, J. R. Ketudat Cairns, L. Ngiwsara & J. Svasti

  2. School of Biochemistry, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima, 30000, Thailand

    J. R. Ketudat Cairns

  3. Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand

    D. Wattanasirichaigoon & P. Suwannarat

  4. Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand

    P. Wasant, J. Kuptanon & S. Liammongkolkul

  5. Division of Medical Genetics, Department of Pediatrics, Queen Sirikit National Institute of Child Health, Bangkok, 10400, Thailand

    S. Pangkanon

  6. Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand

    P. Tanpaiboon

  7. Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand

    T. Rujirawat

  8. Department of Biochemistry, Faculty of Science, Mahidol University, Rama VI Road, Bangkok, 10400, Thailand

    J. Svasti

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  1. S. Keeratichamroen
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  2. J. R. Ketudat Cairns
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  12. J. Svasti
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Corresponding author

Correspondence to J. Svasti.

Additional information

Communicating editor: Douglas Brooks

Competing interests: None declared

References to electronic databases: Hunter syndrome: OMIM 309900. HUGO gene name: IDS. Iduronate-2-sulfatase (IDS): EC 3.1.6.13. Genbank accession number for IDS gene: AH002847.

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Keeratichamroen, S., Ketudat Cairns, J.R., Wattanasirichaigoon, D. et al. Molecular analysis of the iduronate-2-sulfatase gene in Thai patients with Hunter syndrome. J Inherit Metab Dis 31 (Suppl 2), 303–311 (2008). https://doi.org/10.1007/s10545-008-0876-z

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  • DOI: https://doi.org/10.1007/s10545-008-0876-z

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