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Identification and characterisation of mutations underlying Sanfilippo syndrome type B (mucopolysaccharidosis type IIIB)
  1. G-J Lee-Chen1,
  2. S-P Lin2,
  3. S-Z Lin1,
  4. C-K Chuang2,
  5. K-T Hsiao1,
  6. C-F Huang1,
  7. W-C Lien1
  1. 1Department of Biology, National Taiwan Normal University, Taipei, Taiwan, ROC
  2. 2Department of Paediatrics, Division of Genetics, MacKay Memorial Hospital, Taipei, Taiwan, ROC
  1. Correspondence to:
 Dr Lee-Chen, Department of Biology, National Taiwan Normal University, 88 Ting-Chou Road, Section 4, Taipei, Taiwan 117, ROC;
 t43019{at}cc.ntnu.edu.tw

https://doi.org/10.1136/jmg.39.2.e3

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    Sanfilippo syndrome type B or mucopolysaccharidosis type IIIB (MPS IIIB) is an autosomal recessive disorder caused by deficiency of the lysosomal enzyme α-N-acetylglucosaminidase (NAG, EC 3.2.1.50). NAG catalyses the removal of terminal α-N-acetylglucosamine residues from heparan sulphate. In the absence of NAG, partially degraded heparan sulphate accumulates in tissues and is excreted in the urine. Affected subjects show developmental delay, attention deficit disorder, uncontrollable hyperactivity, and aggressive behaviour, followed by progressive dementia with death usually in the late teens.1

    Cloning of the NAG gene and cDNA has enabled studies of the molecular basis of this syndrome.2,3 At present, over 50 different mutations underlying MPS IIIB have been identified, including deletions, insertions, point mutations, and splicing site mutations.3–10 The extensive allelic heterogeneity reflects the wide spectrum of clinical phenotypes reported in MPS IIIB patients.11 In this study, the molecular lesions of six unrelated Chinese patients with MPS IIIB were investigated. Five novel and two previously reported mutations were found. We used transient expression studies to examine the effects of the mutations on NAG catalytic activity, mRNA stability, and protein stability.

    MATERIALS AND METHODS

    DNA preparation and PCR amplification

    The six patients with MPS IIIB had a typical, severe disease course with symptoms and enzyme deficiency diagnosed during early childhood. Patients 773 and 155 died at 8 and 17 years, respectively. The four living patients are 4 to 9 years old, all with moderate mental retardation. Genomic DNA was extracted from whole blood according to standard procedures.12 Polymerase chain reaction (PCR) of NAG exons including adjacent intronic regions was done with primers and conditions listed in table 1. Genomic DNA (100 ng) was used for a 25 μl PCR reaction containing 10 mmol/l Tris, pH 8.3, 50 mmol/l KCl, 0.1% triton X-100, 0.2 mmol/l dNTPs, 0.4 μmol/l of each primer, and 0.5 U …

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