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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2010-9-9
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pubmed:abstractText |
We characterized an autosomal-recessive syndrome of focal epilepsy, dysarthria, and mild to moderate intellectual disability in a consanguineous Arab-Israeli family associated with subtle cortical thickening. We used multipoint linkage analysis to map the causative mutation to a 3.2 Mb interval within 16p13.3 with a LOD score of 3.86. The linked interval contained 160 genes, many of which were considered to be plausible candidates to harbor the disease-causing mutation. To interrogate the interval in an efficient and unbiased manner, we used targeted sequence enrichment and massively parallel sequencing. By prioritizing unique variants that affected protein translation, a pathogenic mutation was identified in TBC1D24 (p.F251L), a gene of unknown function. It is a member of a large gene family encoding TBC domain proteins with predicted function as Rab GTPase activators. We show that TBC1D24 is expressed early in mouse brain and that TBC1D24 protein is a potent modulator of primary axonal arborization and specification in neuronal cells, consistent with the phenotypic abnormality described.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20797691-10999562,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20797691-11591649,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20797691-11731797,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20797691-16252236,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20797691-16855591,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20797691-17189563,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20797691-17406484,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20797691-17696120,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20797691-17934467,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20797691-17982454,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20797691-18199687,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20797691-18275925,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20797691-18537741,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20797691-19182786,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20797691-19377476,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20797691-19435744,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20797691-19477115,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20797691-7984417,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20797691-9582072
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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 |
Sep
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pubmed:issn |
1537-6605
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pubmed:author |
pubmed-author:AfawiZaidZ,
pubmed-author:BahloMelanieM,
pubmed-author:BerkovicSamuel FSF,
pubmed-author:CoffeyAmyA,
pubmed-author:CorbettMark AMA,
pubmed-author:DibbensLeanne MLM,
pubmed-author:GardnerAlison EAE,
pubmed-author:GeczJozefJ,
pubmed-author:JacksonGraeme DGD,
pubmed-author:JollyLachlanL,
pubmed-author:KivitySaraS,
pubmed-author:MulleyJohn CJC,
pubmed-author:OliverKaren LKL,
pubmed-author:ShalataAdelA,
pubmed-author:TanStanleyS,
pubmed-author:WalidSimriS
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pubmed:copyrightInfo |
2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
10
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pubmed:volume |
87
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
371-5
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:20797691-Amino Acid Sequence,
pubmed-meshheading:20797691-Animals,
pubmed-meshheading:20797691-Axons,
pubmed-meshheading:20797691-Carrier Proteins,
pubmed-meshheading:20797691-Cell Shape,
pubmed-meshheading:20797691-Chromosome Mapping,
pubmed-meshheading:20797691-Epilepsies, Partial,
pubmed-meshheading:20797691-Female,
pubmed-meshheading:20797691-GTPase-Activating Proteins,
pubmed-meshheading:20797691-Humans,
pubmed-meshheading:20797691-Infant,
pubmed-meshheading:20797691-Intellectual Disability,
pubmed-meshheading:20797691-Male,
pubmed-meshheading:20797691-Mice,
pubmed-meshheading:20797691-Molecular Sequence Data,
pubmed-meshheading:20797691-Mutation,
pubmed-meshheading:20797691-Neurons,
pubmed-meshheading:20797691-Open Reading Frames,
pubmed-meshheading:20797691-Pedigree,
pubmed-meshheading:20797691-Syndrome
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pubmed:year |
2010
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pubmed:articleTitle |
A focal epilepsy and intellectual disability syndrome is due to a mutation in TBC1D24.
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pubmed:affiliation |
Genetics and Molecular Pathology, SA Pathology, Adelaide, Australia.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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