| First Author | Corbett MA | Year | 2010 |
| Journal | Am J Hum Genet | Volume | 87 |
| Issue | 3 | Pages | 371-5 |
| PubMed ID | 20797691 | Mgi Jnum | J:169187 |
| Mgi Id | MGI:4939988 | Doi | 10.1016/j.ajhg.2010.08.001 |
| Citation | Corbett MA, et al. (2010) A focal epilepsy and intellectual disability syndrome is due to a mutation in TBC1D24. Am J Hum Genet 87(3):371-5 |
| 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. |
