Journal article

A Focal Epilepsy and Intellectual Disability Syndrome Is Due to a Mutation in TBC1D24

Mark 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, Jozef Gecz



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..

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Awarded by National Health and Medical Research Council (NHMRC)

Funding Acknowledgements

We are grateful for the cooperation of the family involved in this study, as well as to Bev Johns for technical assistance and Rob King, Andre Rickers, and Graeme Woolford from Gene Works for help with the resequencing. M.B. and J.G. were supported by the National Health and Medical Research Council (NH&MRC) with a Career Development Award and a Principal Research Fellowship, respectively. This project was supported by NH&MRC program grant 400121 and also by International Science Linkages, established under the Australian Government's innovation statement, "Backing Australia's Ability."