A focal Eeilepsy and intellectual disability syndrome is due to a mutation in TBC1D24

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dc.contributor.authorBahlo, M.
dc.contributor.authorJolly, L.
dc.contributor.authorAfawi, Z.
dc.contributor.authorGardner, A.
dc.contributor.authorOliver, K.
dc.contributor.authorTan, S.
dc.contributor.authorCoffey, A.
dc.contributor.authorMulley, J.
dc.contributor.authorDibbens, L.
dc.contributor.authorSimri, W.
dc.contributor.authorShalata, A.
dc.contributor.authorKivity, S.
dc.contributor.authorJackson, G.
dc.contributor.authorBerkovic, S.
dc.contributor.authorGecz, J.
dc.contributor.authorCorbett, M.
dc.date.issued2010
dc.description.abstractWe 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.
dc.description.statementofresponsibilityMark A. Corbett, Melanie Bahlo, Lachlan Jolly, Zaid Afawi, Alison E. Gardner, Karen L. Oliver, Stanley Tan, Amy Coffey, John C. Mulley, Leanne M. Dibbens, Walid Simri, Adel Shalata, Sara Kivity, Graeme D. Jackson, Samuel F. Berkovic, and Jozef Gecz
dc.identifier.citationAmerican Journal of Human Genetics, 2010; 87(3):371-375
dc.identifier.doi10.1016/j.ajhg.2010.08.001
dc.identifier.issn0002-9297
dc.identifier.issn1537-6605
dc.identifier.orcidJolly, L. [0000-0003-4538-2658]
dc.identifier.orcidGardner, A. [0009-0009-7321-1697]
dc.identifier.orcidGecz, J. [0000-0002-7884-6861]
dc.identifier.orcidCorbett, M. [0000-0001-9298-3072]
dc.identifier.urihttp://hdl.handle.net/2440/62378
dc.language.isoen
dc.publisherUniv Chicago Press
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/400121
dc.rights© 2010 The American Society of Human Genetics
dc.source.urihttps://doi.org/10.1016/j.ajhg.2010.08.001
dc.subjectNeurons
dc.subjectAxons
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectEpilepsies, Partial
dc.subjectSyndrome
dc.subjectGTPase-Activating Proteins
dc.subjectCarrier Proteins
dc.subjectMembrane Proteins
dc.subjectNerve Tissue Proteins
dc.subjectChromosome Mapping
dc.subjectPedigree
dc.subjectCell Shape
dc.subjectAmino Acid Sequence
dc.subjectMutation
dc.subjectOpen Reading Frames
dc.subjectMolecular Sequence Data
dc.subjectInfant
dc.subjectFemale
dc.subjectMale
dc.subjectIntellectual Disability
dc.titleA focal Eeilepsy and intellectual disability syndrome is due to a mutation in TBC1D24
dc.typeJournal article
pubs.publication-statusPublished

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