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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2010-2-1
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pubmed:abstractText |
We recently identified KCNC3, encoding the Kv3.3 voltage-gated potassium channel, as the gene mutated in SCA13. One g.10684G>A (p.Arg420His) mutation caused late-onset ataxia resulting in a nonfunctional channel subunit with dominant-negative properties. A French early-onset pedigree with mild mental retardation segregated a g.10767T>C (p.Phe448Leu) mutation. This mutation changed the relative stability of the channel's open conformation. Coding exons were amplified and sequenced in 260 autosomal-dominant ataxia index cases of European descent. Functional analyses were performed using expression in Xenopus oocytes. The previously identified p.Arg420His mutation occurred in three families with late-onset ataxia. A novel mutation g.10693G>A (p.Arg423His) was identified in two families with early-onset. In one pedigree, a novel g.10522G>A (p.Arg366His) sequence variant was seen in one index case but did not segregate with affected status in the respective family. In a heterologous expression system, the p.Arg423His mutation exhibited dominant-negative properties. The p.Arg420His mutation, which results in a nonfunctional channel subunit, was recurrent and associated with late-onset progressive ataxia. In two families the p.Arg423His mutation was associated with early-onset slow-progressive ataxia. Despite a phenotype reminiscent of the p.Phe448Leu mutation, segregating in a large early-onset French pedigree, the p.Arg423His mutation resulted in a nonfunctional subunit with a strong dominant-negative effect.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19953606-10712820,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19953606-10820125,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19953606-14676051,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19953606-16135769,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19953606-16429157,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19953606-16501573,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19953606-17330043,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19953606-18037885,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19953606-1846229,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19953606-18539595,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19953606-18769991,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19953606-18824591,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19953606-8663992,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19953606-8663993
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1098-1004
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pubmed:author |
pubmed-author:BürkKatrinK,
pubmed-author:BriceAlexisA,
pubmed-author:DürrAlexandraA,
pubmed-author:FigueroaKarla PKP,
pubmed-author:ForlaniSylvieS,
pubmed-author:GaribyanVartanV,
pubmed-author:MinassianNatali ANA,
pubmed-author:PapazianDiane MDM,
pubmed-author:PulstStefan MSM,
pubmed-author:StevaninGiovanniG,
pubmed-author:StrzelczykAdamA,
pubmed-author:WatersMichaelM
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pubmed:copyrightInfo |
(c) 2009 Wiley-Liss, Inc.
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pubmed:issnType |
Electronic
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pubmed:volume |
31
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
191-6
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pubmed:dateRevised |
2011-7-22
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pubmed:meshHeading |
pubmed-meshheading:19953606-Adolescent,
pubmed-meshheading:19953606-Adult,
pubmed-meshheading:19953606-Aged,
pubmed-meshheading:19953606-Animals,
pubmed-meshheading:19953606-Biophysical Phenomena,
pubmed-meshheading:19953606-Case-Control Studies,
pubmed-meshheading:19953606-Child, Preschool,
pubmed-meshheading:19953606-Demography,
pubmed-meshheading:19953606-Family,
pubmed-meshheading:19953606-Friedreich Ataxia,
pubmed-meshheading:19953606-Genes, Dominant,
pubmed-meshheading:19953606-Humans,
pubmed-meshheading:19953606-Infant, Newborn,
pubmed-meshheading:19953606-Magnetic Resonance Imaging,
pubmed-meshheading:19953606-Middle Aged,
pubmed-meshheading:19953606-Mutation,
pubmed-meshheading:19953606-Phenotype,
pubmed-meshheading:19953606-Shaw Potassium Channels,
pubmed-meshheading:19953606-Xenopus
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pubmed:year |
2010
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pubmed:articleTitle |
KCNC3: phenotype, mutations, channel biophysics-a study of 260 familial ataxia patients.
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pubmed:affiliation |
Department of Neurology, University of Utah, Salt Lake City, Utah, USA.
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pubmed:publicationType |
Journal Article
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