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Article: Molecular investigations of a novel iduronate-2-sulfatase mutant in a Chinese patient
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TitleMolecular investigations of a novel iduronate-2-sulfatase mutant in a Chinese patient
 
AuthorsLau, KC1
Lam, CW1
 
Issue Date2008
 
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/cca
 
CitationClinica Chimica Acta, 2008, v. 392 n. 1-2, p. 8-10 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.cca.2008.02.009
 
AbstractBackground: Molecular investigations of iduronate-2-sulfatase (IDS) mutants for the X-linked lysosomal storage disease mucopolysaccharidosis type II (MPS II, Hunter disease), commonly depends on transient expression studies to verify a single nucleotide change to be pathogenic. In 2 severely affected patients, IDS missense mutations, c.1016T>C (novel) and c.1016T>G (known) were identified predicting the substitution of an ambivalent cyclic proline and a hydrophilic arginine respectively for the hydrophobic leucine at residue 339. We hypothesized that residue Leu339 may be functionally critical. Methods: We performed a study for the 2 mutations by in-situ mutagenesis, in vitro expression, and functional analysis. Results: Transient expression revealed that both the missense variants had stable mRNA but their residual enzyme activities remained < 2.5% of normal level. The effect of the missense mutations on protein expression was detected by Western blot analysis. Both the missense mutations synthesized the precursor form but had reduced mature form of IDS. Conclusion: The novel mutation p.L339P is a disease-causing mutation affecting maturation of the protein. © 2008 Elsevier B.V. All rights reserved.
 
ISSN0009-8981
2013 Impact Factor: 2.764
2013 SCImago Journal Rankings: 1.039
 
DOIhttp://dx.doi.org/10.1016/j.cca.2008.02.009
 
ISI Accession Number IDWOS:000256581000002
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorLau, KC
 
dc.contributor.authorLam, CW
 
dc.date.accessioned2012-05-29T06:13:42Z
 
dc.date.available2012-05-29T06:13:42Z
 
dc.date.issued2008
 
dc.description.abstractBackground: Molecular investigations of iduronate-2-sulfatase (IDS) mutants for the X-linked lysosomal storage disease mucopolysaccharidosis type II (MPS II, Hunter disease), commonly depends on transient expression studies to verify a single nucleotide change to be pathogenic. In 2 severely affected patients, IDS missense mutations, c.1016T>C (novel) and c.1016T>G (known) were identified predicting the substitution of an ambivalent cyclic proline and a hydrophilic arginine respectively for the hydrophobic leucine at residue 339. We hypothesized that residue Leu339 may be functionally critical. Methods: We performed a study for the 2 mutations by in-situ mutagenesis, in vitro expression, and functional analysis. Results: Transient expression revealed that both the missense variants had stable mRNA but their residual enzyme activities remained < 2.5% of normal level. The effect of the missense mutations on protein expression was detected by Western blot analysis. Both the missense mutations synthesized the precursor form but had reduced mature form of IDS. Conclusion: The novel mutation p.L339P is a disease-causing mutation affecting maturation of the protein. © 2008 Elsevier B.V. All rights reserved.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationClinica Chimica Acta, 2008, v. 392 n. 1-2, p. 8-10 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.cca.2008.02.009
 
dc.identifier.doihttp://dx.doi.org/10.1016/j.cca.2008.02.009
 
dc.identifier.epage10
 
dc.identifier.isiWOS:000256581000002
 
dc.identifier.issn0009-8981
2013 Impact Factor: 2.764
2013 SCImago Journal Rankings: 1.039
 
dc.identifier.issue1-2
 
dc.identifier.pmid18331837
 
dc.identifier.scopuseid_2-s2.0-42749090539
 
dc.identifier.spage8
 
dc.identifier.urihttp://hdl.handle.net/10722/148557
 
dc.identifier.volume392
 
dc.languageeng
 
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/cca
 
dc.publisher.placeNetherlands
 
dc.relation.ispartofClinica Chimica Acta
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAdolescent
 
dc.subject.meshAdult
 
dc.subject.meshAmino Acid Substitution
 
dc.subject.meshCell Line
 
dc.subject.meshChild, Preschool
 
dc.subject.meshChina
 
dc.subject.meshExons
 
dc.subject.meshHumans
 
dc.subject.meshIduronate Sulfatase - Chemistry - Genetics - Metabolism
 
dc.subject.meshMucopolysaccharidosis Ii - Etiology - Genetics
 
dc.subject.meshMutagenesis, Site-Directed
 
dc.subject.meshMutation, Missense
 
dc.subject.meshPoint Mutation
 
dc.titleMolecular investigations of a novel iduronate-2-sulfatase mutant in a Chinese patient
 
dc.typeArticle
 
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Author Affiliations
  1. Prince of Wales Hospital Hong Kong