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Molecular analysis of the iduronate‐2‐sulfatase gene in Thai patients with Hunter syndrome
Author(s) -
Keeratichamroen S.,
Ketudat Cairns J. R.,
Wattanasirichaigoon D.,
Wasant P.,
Ngiwsara L.,
Suwannarat P.,
Pangka S.,
Kupta J.,
Tanpaiboon P.,
Rujirawat T.,
Liammongkolkul S.,
Svasti J.
Publication year - 2008
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-008-0876-z
Subject(s) - hunter syndrome , mucopolysaccharidosis type ii , missense mutation , nonsense mutation , gene , genetics , biology , mutation , microbiology and biotechnology , nonsense mediated decay , rna splicing , medicine , disease , enzyme replacement therapy , rna
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.