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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)782-787
Number of pages6
JournalAnnals of Neurology
Volume75
Issue number5
DOIs
Publication statusPublished - 2014

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Partial Epilepsy
Sirolimus
Mutation
Brain
Tuberous Sclerosis
Epilepsy
Phenotype
Growth
Genes
Therapeutics

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Scheffer, I. E., Heron, S. E., Regan, B. M., Mandelstam, S., Crompton, D. E., Hodgson, B. L., ... Dibbens, L. M. (2014). Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations. Annals of Neurology, 75(5), 782-787. https://doi.org/10.1002/ana.24126

Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations. / Scheffer, Ingrid E.; Heron, Sarah E.; Regan, Brigid M.; Mandelstam, Simone; Crompton, Douglas E.; Hodgson, Bree L.; Licchetta, Laura; Provini, Federica; Bisulli, Francesca; Vadlamudi, Lata; Gecz, Jozef; Connelly, Alan; Tinuper, Paolo; Ricos, Michael G.; Berkovic, Samuel F.; Dibbens, Leanne M.

In: Annals of Neurology, Vol. 75, No. 5, 2014, p. 782-787.

Research output: Contribution to journalArticle

Scheffer, IE, Heron, SE, Regan, BM, Mandelstam, S, Crompton, DE, Hodgson, BL, Licchetta, L, Provini, F, Bisulli, F, Vadlamudi, L, Gecz, J, Connelly, A, Tinuper, P, Ricos, MG, Berkovic, SF & Dibbens, LM 2014, 'Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations', Annals of Neurology, vol. 75, no. 5, pp. 782-787. https://doi.org/10.1002/ana.24126
Scheffer, Ingrid E. ; Heron, Sarah E. ; Regan, Brigid M. ; Mandelstam, Simone ; Crompton, Douglas E. ; Hodgson, Bree L. ; Licchetta, Laura ; Provini, Federica ; Bisulli, Francesca ; Vadlamudi, Lata ; Gecz, Jozef ; Connelly, Alan ; Tinuper, Paolo ; Ricos, Michael G. ; Berkovic, Samuel F. ; Dibbens, Leanne M. / Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations. In: Annals of Neurology. 2014 ; Vol. 75, No. 5. pp. 782-787.
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