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Article: Molecular investigations of a novel iduronate-2-sulfatase mutant in a Chinese patient

TitleMolecular investigations of a novel iduronate-2-sulfatase mutant in a Chinese patient
Authors
Issue Date2008
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/cca
Citation
Clinica Chimica Acta, 2008, v. 392 n. 1-2, p. 8-10 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/148557
ISSN
2014 Impact Factor: 2.824
2013 SCImago Journal Rankings: 1.039
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLau, KCen_US
dc.contributor.authorLam, CWen_US
dc.date.accessioned2012-05-29T06:13:42Z-
dc.date.available2012-05-29T06:13:42Z-
dc.date.issued2008en_US
dc.identifier.citationClinica Chimica Acta, 2008, v. 392 n. 1-2, p. 8-10en_US
dc.identifier.issn0009-8981en_US
dc.identifier.urihttp://hdl.handle.net/10722/148557-
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.en_US
dc.languageengen_US
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/ccaen_US
dc.relation.ispartofClinica Chimica Actaen_US
dc.subject.meshAdolescenten_US
dc.subject.meshAdulten_US
dc.subject.meshAmino Acid Substitutionen_US
dc.subject.meshCell Lineen_US
dc.subject.meshChild, Preschoolen_US
dc.subject.meshChinaen_US
dc.subject.meshExonsen_US
dc.subject.meshHumansen_US
dc.subject.meshIduronate Sulfatase - Chemistry - Genetics - Metabolismen_US
dc.subject.meshMucopolysaccharidosis Ii - Etiology - Geneticsen_US
dc.subject.meshMutagenesis, Site-Directeden_US
dc.subject.meshMutation, Missenseen_US
dc.subject.meshPoint Mutationen_US
dc.titleMolecular investigations of a novel iduronate-2-sulfatase mutant in a Chinese patienten_US
dc.typeArticleen_US
dc.identifier.emailLam, CW:ching-wanlam@pathology.hku.hken_US
dc.identifier.authorityLam, CW=rp00260en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.cca.2008.02.009en_US
dc.identifier.pmid18331837en_US
dc.identifier.scopuseid_2-s2.0-42749090539en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-42749090539&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume392en_US
dc.identifier.issue1-2en_US
dc.identifier.spage8en_US
dc.identifier.epage10en_US
dc.identifier.isiWOS:000256581000002-
dc.publisher.placeNetherlandsen_US

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