Source:http://linkedlifedata.com/resource/pubmed/id/16541386
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2006-3-21
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pubmed:databankReference | |
pubmed:abstractText |
Mutations in KCNJ2, the gene encoding the human inward rectifier potassium channel Kir2.1, have been identified in Andersen syndrome (or Andersen-Tawil syndrome), an inherited disorder characterized by periodic paralysis, cardiac arrhythmias, and dysmorphic features. We identified and characterized two novel KCNJ2 mutations (c.220A>G/p.T74A and c.443G>C/p.G144A) associated with Andersen syndrome. Heterologous expression of a recombinant wild type human KCNJ2 cDNA (WT-KCNJ2) in HEK-293 cells results in robust inward rectifying currents, but we did not observe measurable currents from cells expressing either mutant. Cells co-transfected with WT-KCNJ2 and either mutant exhibited substantially lower whole-cell current amplitude consistent with a dominant-negative suppression of WT-KCNJ2 by the mutant channels. Both p.T74A and p.G144A exhibit robust plasma membrane expression, but a third previously reported allele (p.C101R) exhibited impaired trafficking. Our results demonstrate functional consequences of two novel trafficking-competent KCNJ2 mutations associated with Andersen syndrome and expand our knowledge of allelic diversity in this disease.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1098-1004
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pubmed:author | |
pubmed:copyrightInfo |
Published 2006 Wiley-Liss, Inc.
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pubmed:issnType |
Electronic
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pubmed:volume |
27
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
388
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pubmed:dateRevised |
2007-12-3
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pubmed:meshHeading |
pubmed-meshheading:16541386-Amino Acid Sequence,
pubmed-meshheading:16541386-Andersen Syndrome,
pubmed-meshheading:16541386-Child,
pubmed-meshheading:16541386-DNA Mutational Analysis,
pubmed-meshheading:16541386-Electrocardiography,
pubmed-meshheading:16541386-Female,
pubmed-meshheading:16541386-Gene Expression,
pubmed-meshheading:16541386-Humans,
pubmed-meshheading:16541386-Male,
pubmed-meshheading:16541386-Models, Molecular,
pubmed-meshheading:16541386-Molecular Sequence Data,
pubmed-meshheading:16541386-Mutation,
pubmed-meshheading:16541386-Pedigree,
pubmed-meshheading:16541386-Potassium Channels, Inwardly Rectifying,
pubmed-meshheading:16541386-Protein Transport
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pubmed:year |
2006
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pubmed:articleTitle |
Trafficking-competent and trafficking-defective KCNJ2 mutations in Andersen syndrome.
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pubmed:affiliation |
Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37027-0275, USA.
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pubmed:publicationType |
Journal Article,
Case Reports,
Research Support, N.I.H., Extramural
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