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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2009-6-2
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pubmed:abstractText |
Genetic variants of the SLC6A3 gene that encodes the human dopamine transporter (DAT) have been linked to a variety of neuropsychiatric disorders, particularly attention deficit hyperactivity disorder. In addition, the homozygous Slc6a3 knockout mouse displays a hyperactivity phenotype. Here, we analyzed 2 unrelated consanguineous families with infantile parkinsonism-dystonia (IPD) syndrome and identified homozygous missense SLC6A3 mutations (p.L368Q and p.P395L) in both families. Functional studies demonstrated that both mutations were loss-of-function mutations that severely reduced levels of mature (85-kDa) DAT while having a differential effect on the apparent binding affinity of dopamine. Thus, in humans, loss-of-function SLC6A3 mutations that impair DAT-mediated dopamine transport activity are associated with an early-onset complex movement disorder. Identification of the molecular basis of IPD suggests SLC6A3 as a candidate susceptibility gene for other movement disorders associated with parkinsonism and/or dystonic features.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19478460-12359863,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19478460-12773538,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19478460-14660644,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19478460-15024013,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19478460-15097293,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19478460-15140185,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19478460-15159499,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19478460-15174010,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19478460-15260953,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19478460-15480838,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19478460-15845424,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19478460-1599505,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19478460-16041361,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19478460-16722244,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19478460-16880288,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19478460-17197367,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19478460-17250655,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19478460-17687333,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19478460-17690069,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19478460-17690258,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19478460-18088380,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19478460-18570870,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19478460-18614672,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19478460-19504720,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19478460-8628395
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1558-8238
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pubmed:author |
pubmed-author:ChengShu-YuanSY,
pubmed-author:GissenPaulP,
pubmed-author:HealesSimon J RSJ,
pubmed-author:JardinePhilipP,
pubmed-author:KurianManju AMA,
pubmed-author:LiYanY,
pubmed-author:MaherEamonn RER,
pubmed-author:MeyerEstherE,
pubmed-author:MordekarSantosh RSR,
pubmed-author:MorganNeil VNV,
pubmed-author:PashaShanazS,
pubmed-author:ReithMaarten E AME,
pubmed-author:TeeLouiseL,
pubmed-author:WassmerEvangelineE,
pubmed-author:ZhenJuanJ
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pubmed:issnType |
Electronic
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pubmed:volume |
119
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1595-603
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:19478460-Amino Acid Sequence,
pubmed-meshheading:19478460-Animals,
pubmed-meshheading:19478460-Base Sequence,
pubmed-meshheading:19478460-Child,
pubmed-meshheading:19478460-Child, Preschool,
pubmed-meshheading:19478460-Chromosomes, Human, Pair 5,
pubmed-meshheading:19478460-Dopamine Plasma Membrane Transport Proteins,
pubmed-meshheading:19478460-Dystonia,
pubmed-meshheading:19478460-Female,
pubmed-meshheading:19478460-Homozygote,
pubmed-meshheading:19478460-Humans,
pubmed-meshheading:19478460-Male,
pubmed-meshheading:19478460-Microsatellite Repeats,
pubmed-meshheading:19478460-Molecular Sequence Data,
pubmed-meshheading:19478460-Mutation,
pubmed-meshheading:19478460-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:19478460-Parkinsonian Disorders,
pubmed-meshheading:19478460-Pedigree,
pubmed-meshheading:19478460-Phenotype,
pubmed-meshheading:19478460-Sequence Alignment,
pubmed-meshheading:19478460-Sequence Homology, Amino Acid
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pubmed:year |
2009
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pubmed:articleTitle |
Homozygous loss-of-function mutations in the gene encoding the dopamine transporter are associated with infantile parkinsonism-dystonia.
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pubmed:affiliation |
Department of Medical and Molecular Genetics, University of Birmingham School of Medicine, Institute of Biomedical Research, Birmingham, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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