TY - JOUR
T1 - Detection of hunter syndrome (mucopolysaccharidosis type II) in Taiwanese
T2 - Biochemical and linkage studies of the iduronate-2-sulfatase gene defects in MPS II patients and carriers
AU - Lin, Shuan Pei
AU - Chang, Jui Hung
AU - Lee-Chen, Guey Jen
AU - Lin, Dar Shong
AU - Lin, Hsiang Yu
AU - Chuang, Chih Kuang
N1 - Funding Information:
We thank the patients' families for their support. In addition, we would like to express our thanks to Dr. Mary Jeanne Buttrey for her revision of this article. Taiwan Foundation for Rare Disorders is also acknowledged for providing thesis scholarship. This study was supported by the following research grants MMH # 9245 and MMH-E-94004 from Mackay Memorial Hospital, NSC-89-2314-B-195-003 and NSC-90-2311-B-003-004 from the National Science Council, Executive Yuan, R.O.C.
PY - 2006/7/15
Y1 - 2006/7/15
N2 - Background: Hunter syndrome (mucopolysaccharidosis type II) is an X-linked recessive lysosomal storage disease caused by a defect of the iduronate-2-sulfatase (IDS) gene. The result is impaired IDS enzyme function. Methods: To characterize the biochemical and molecular defects in IDS-deficient patients and their families, we measured IDS enzyme activity by fluorimetric enzyme assay and identified the IDS gene mutations in 14 unrelated Taiwanese patients with varying clinical phenotypes. In addition, haplotype analysis was also performed. Results: Three novel (IVS2 + 1G > C, 1055del12, and G489D) and 7 previously reported (N63K, P228L, K347E, R468Q, R468W, I485R, and 1241delAG) mutations were found. Together R468Q and R468W account for 42.8% mutations found in our patients. Haplotype analysis using IDS flanking markers DXS1113 and DXS1123 revealed that the unrelated R468Q alleles were independent in origin whereas the unrelated R468W alleles are probably of the same origin. The R468Q mutation in patient 1150 and I485R mutation in patient 710 occurred de novo in male meioses. Once the mutation in a family was identified, restriction analysis was also performed for rapid diagnosis of female carriers in 8 families. Leukocyte IDS measurement revealed significantly wide range of IDS activity in normal controls and MPS II carriers (19.2∼70.6 vs. 8.4∼26.6 nmol/h/mg cell protein). The average leukocyte IDS activity of normal controls (n = 43) was 43.9 ± 13.3 nmol/h/mg protein, whereas patients with MPS II (n = 14) had < 5% of mean normal IDS activity (0.9 ± 0.6 nmol/h/mg protein), and carriers (n = 13) had a mean activity of 17.5 (± 5.7) nmol/h/mg protein. The mean leukocyte IDS activity in female carriers was less than a half of the normal level. Conclusion: Due to a small overlapping range of normal and carriers, the level of enzyme activity cannot be used alone for carrier detection.
AB - Background: Hunter syndrome (mucopolysaccharidosis type II) is an X-linked recessive lysosomal storage disease caused by a defect of the iduronate-2-sulfatase (IDS) gene. The result is impaired IDS enzyme function. Methods: To characterize the biochemical and molecular defects in IDS-deficient patients and their families, we measured IDS enzyme activity by fluorimetric enzyme assay and identified the IDS gene mutations in 14 unrelated Taiwanese patients with varying clinical phenotypes. In addition, haplotype analysis was also performed. Results: Three novel (IVS2 + 1G > C, 1055del12, and G489D) and 7 previously reported (N63K, P228L, K347E, R468Q, R468W, I485R, and 1241delAG) mutations were found. Together R468Q and R468W account for 42.8% mutations found in our patients. Haplotype analysis using IDS flanking markers DXS1113 and DXS1123 revealed that the unrelated R468Q alleles were independent in origin whereas the unrelated R468W alleles are probably of the same origin. The R468Q mutation in patient 1150 and I485R mutation in patient 710 occurred de novo in male meioses. Once the mutation in a family was identified, restriction analysis was also performed for rapid diagnosis of female carriers in 8 families. Leukocyte IDS measurement revealed significantly wide range of IDS activity in normal controls and MPS II carriers (19.2∼70.6 vs. 8.4∼26.6 nmol/h/mg cell protein). The average leukocyte IDS activity of normal controls (n = 43) was 43.9 ± 13.3 nmol/h/mg protein, whereas patients with MPS II (n = 14) had < 5% of mean normal IDS activity (0.9 ± 0.6 nmol/h/mg protein), and carriers (n = 13) had a mean activity of 17.5 (± 5.7) nmol/h/mg protein. The mean leukocyte IDS activity in female carriers was less than a half of the normal level. Conclusion: Due to a small overlapping range of normal and carriers, the level of enzyme activity cannot be used alone for carrier detection.
KW - Hunter syndrome
KW - IDS gene
KW - Iduronate-2-sulfatase
KW - Mucopolysaccharidosis type II
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U2 - 10.1016/j.cca.2006.01.001
DO - 10.1016/j.cca.2006.01.001
M3 - Article
C2 - 16480701
AN - SCOPUS:33646867421
SN - 0009-8981
VL - 369
SP - 29
EP - 34
JO - Clinica Chimica Acta
JF - Clinica Chimica Acta
IS - 1
ER -