Detection of hunter syndrome (mucopolysaccharidosis type II) in Taiwanese: Biochemical and linkage studies of the iduronate-2-sulfatase gene defects in MPS II patients and carriers

Shuan Pei Lin, Jui Hung Chang, Guey-Jen Lee, Dar Shong Lin, Hsiang Yu Lin, Chih Kuang Chuang

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)29-34
Number of pages6
JournalClinica Chimica Acta
Volume369
Issue number1
DOIs
Publication statusPublished - 2006 Jul 15

Fingerprint

Iduronate Sulfatase
Iduronic Acid
Mucopolysaccharidosis II
Sulfatases
Genes
Defects
Mutation
Leukocytes
Enzyme activity
Haplotypes
Enzymes
Alleles
Mucopolysaccharidosis I
Lysosomal Storage Diseases
Proteins
Meiosis
Enzyme Assays

Keywords

  • Hunter syndrome
  • IDS gene
  • Iduronate-2-sulfatase
  • Mucopolysaccharidosis type II

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Detection of hunter syndrome (mucopolysaccharidosis type II) in Taiwanese : Biochemical and linkage studies of the iduronate-2-sulfatase gene defects in MPS II patients and carriers. / Lin, Shuan Pei; Chang, Jui Hung; Lee, Guey-Jen; Lin, Dar Shong; Lin, Hsiang Yu; Chuang, Chih Kuang.

In: Clinica Chimica Acta, Vol. 369, No. 1, 15.07.2006, p. 29-34.

Research output: Contribution to journalArticle

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title = "Detection of hunter syndrome (mucopolysaccharidosis type II) in Taiwanese: Biochemical and linkage studies of the iduronate-2-sulfatase gene defects in MPS II patients and carriers",
abstract = "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.",
keywords = "Hunter syndrome, IDS gene, Iduronate-2-sulfatase, Mucopolysaccharidosis type II",
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T2 - Biochemical and linkage studies of the iduronate-2-sulfatase gene defects in MPS II patients and carriers

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AU - Chang, Jui Hung

AU - Lee, Guey-Jen

AU - Lin, Dar Shong

AU - Lin, Hsiang Yu

AU - Chuang, Chih Kuang

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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.

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