A Focal Epilepsy and Intellectual Disability Syndrome Is Due to a Mutation in TBC1D24
- Author(s)
- Corbett, MA; Bahlo, M; Jolly, L; Afawi, Z; Gardner, AE; Oliver, KL; Tan, S; Coffey, A; Mulley, JC; Dibbens, LM; Simri, W; Shalata, A; Kivity, S; Jackson, GD; Berkovic, SF; Gecz, J;
- Details
- Publication Year 2010-09-10,Volume 87,Issue #3,Page 371-375
- Journal Title
- AMERICAN JOURNAL OF HUMAN GENETICS
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- CELL PRESS
- Keywords
- MENTAL-RETARDATION; SELECTION
- Publisher's Version
- https://doi.org/10.1016/j.ajhg.2010.08.001
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2010-09-10 12:00:00