Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations

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. DEP...

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Bibliographic Details
Published in:Annals of neurology 2014-05, Vol.75 (5), p.782-787
Main Authors: 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.
Format: Article
Language:English
Subjects:
Adult
Brain - abnormalities
Child
Epilepsies, Partial - diagnosis
Epilepsies, Partial - genetics
Epilepsy
Female
Humans
Male
Mutation
Mutation - genetics
Pedigree
Repressor Proteins - genetics
TOR Serine-Threonine Kinases - genetics
Young Adult
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Summary: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
ISSN:0364-5134
1531-8249
DOI:10.1002/ana.24126