Journal article

Mutations in Mammalian Target of Rapamycin Regulator DEPDC5 Cause Focal Epilepsy with Brain Malformations

Ingrid E Scheffer, Sarah E Heron, Brigid M Regan, Simone Mandelstam, Douglas E Crompton, Bree L Hodgson, Laura Licchetta, Federica Provini, Francesca Bisulli, Lata Vadlamudi, Jozef Gecz, Alan Connelly, Paolo Tinuper, Michael G Ricos, Samuel F Berkovic, Leanne M Dibbens



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..

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Awarded by National Health and Medical Research Council of Australia

Awarded by Australian Research Council

Funding Acknowledgements

This work was supported by the National Health and Medical Research Council of Australia (Program Grant 628952 to S. F. B., I. E. S., J.G., and L. M. D., Practitioner Fellowship 1006110 to I. E. S., Early Career Fellowship 1016715 to S. E. H., and Career Development Fellowship 1032603 to L. M. D.), UCB Pharma (unrestricted educational grant 2006-2009 to D. E. C.), and the Australian Research Council Discovery Project 120100285 to (I.E.S.).