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
2011 Impact Factor: 2.535
2011 SCImago Journal Rankings: 0.189
DOIhttp://dx.doi.org/10.1016/j.cca.2008.02.009
ReferencesReferences in Scopus
DC Field
Value
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
2011 Impact Factor: 2.535
2011 SCImago Journal Rankings: 0.189
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
Author Affiliations
  1. Prince of Wales Hospital Hong Kong