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. and Dibbens, Leanne M. (2014) Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations. Annals of Neurology, 75 5: 782-787. doi:10.1002/ana.24126


Author 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.
Title Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations
Formatted title
Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations
Journal name Annals of Neurology   Check publisher's open access policy
ISSN 1531-8249
0364-5134
Publication date 2014-05
Year available 2014
Sub-type Article (original research)
DOI 10.1002/ana.24126
Open Access Status
Volume 75
Issue 5
Start page 782
End page 787
Total pages 6
Place of publication Hoboken, NJ, United States
Publisher John Wiley and Sons
Collection year 2015
Language eng
Formatted 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.
Keyword DEPDC5
Familial focal epilepsy
Brain malformations
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 50 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 50 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 24 Jun 2014, 04:08:07 EST by System User on behalf of School of Medicine