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

2014-04-14

Scheffer, Ingrid E

Heron, Sarah E

Regan, Brigid M

Mandelstam, Simone A

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

Journal Article

10.1002/ana.24126

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.

link

Annals of Neurology 2014; 75(5): 782-7

Annals of Neurology