| Affiliation: | 1. Epilepsy Research Centre, Department of Medicine, University of Melbourne, Melbourne, Australia;2. Florey Institute of Neuroscience and Mental Health, Melbourne, Australia;3. Department of Paediatrics, University of Melbourne, Melbourne, Australia;4. Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia;5. Sansom Institute for Health Research, University of South Australia, Adelaide, Australia;6. Department of Radiology, University of Melbourne, Melbourne, Australia;7. Department of Neurology, Northern Health, Melbourne, Australia;8. IRCCS, Institute of Neurological Science, University of Bologna, Bologna, Italy;9. Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy;10. School of Medicine, University of Queensland and Department of Neurology, Brisbane, Australia;11. School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, Australia;12. Department of Medicine, Austin Health, University of Melbourne, Melbourne, Australia |
| Abstract: | We recently identified DEPDC5 as the gene for familial focal epilepsy with variable foci and found mutations in >10% of small families with nonlesional focal epilepsy. Here we show that DEPDC5 mutations are associated with both lesional and nonlesional epilepsies, even within the same family. DEPDC5‐associated malformations include bottom‐of‐the‐sulcus dysplasia (3 members from 2 families), and focal band heterotopia (1 individual). DEPDC5 negatively regulates the mammalian target of rapamycin (mTOR) pathway, which plays a key role in cell growth. The clinicoradiological phenotypes associated with DEPDC5 mutations share features with the archetypal mTORopathy, tuberous sclerosis, raising the possibility of therapies targeted to this pathway. Ann Neurol 2014;75:782–787 |
